<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:711d77e0-1ffe-423a-8c18-4b17c697ec1c,g:8cabc86b-e65e-476d-80a6-d47d8cc845d6-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.ardelyx.com/role/CONDENSEDBALANCESHEETS" xlink:type="simple" xlink:href="ardx-20250331.xsd#CONDENSEDBALANCESHEETS"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/CONDENSEDBALANCESHEETS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_37293994-a01e-4811-b17c-8873e20fc88d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_830daf9a-290b-4c0e-a79d-93f98054c1d8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_37293994-a01e-4811-b17c-8873e20fc88d" xlink:to="loc_us-gaap_LiabilitiesCurrent_830daf9a-290b-4c0e-a79d-93f98054c1d8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_9d50dbd2-2655-4909-850d-7d366beb2b9e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_37293994-a01e-4811-b17c-8873e20fc88d" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_9d50dbd2-2655-4909-850d-7d366beb2b9e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_8928d31c-4c64-411f-add8-48ed6cfbef90" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_37293994-a01e-4811-b17c-8873e20fc88d" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_8928d31c-4c64-411f-add8-48ed6cfbef90" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_DeferredRoyaltyObligationNoncurrent_ed057afd-8759-43e3-9fcc-ea94318154b2" xlink:href="ardx-20250331.xsd#ardx_DeferredRoyaltyObligationNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_37293994-a01e-4811-b17c-8873e20fc88d" xlink:to="loc_ardx_DeferredRoyaltyObligationNoncurrent_ed057afd-8759-43e3-9fcc-ea94318154b2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermLoansPayable_07e4032d-8bad-4bbf-9266-1e74be7e2c32" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermLoansPayable"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_37293994-a01e-4811-b17c-8873e20fc88d" xlink:to="loc_us-gaap_LongTermLoansPayable_07e4032d-8bad-4bbf-9266-1e74be7e2c32" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_3575f371-3632-42c6-ae6a-0b384361b270" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_fbc6937b-eb69-485e-a561-ec3e6a79c32d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_3575f371-3632-42c6-ae6a-0b384361b270" xlink:to="loc_us-gaap_Liabilities_fbc6937b-eb69-485e-a561-ec3e6a79c32d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_75e4d0be-c78f-4f17-a34b-6457a1b794a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_3575f371-3632-42c6-ae6a-0b384361b270" xlink:to="loc_us-gaap_CommitmentsAndContingencies_75e4d0be-c78f-4f17-a34b-6457a1b794a2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_2b8c6175-6210-4094-b6fb-778612f024f9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_3575f371-3632-42c6-ae6a-0b384361b270" xlink:to="loc_us-gaap_StockholdersEquity_2b8c6175-6210-4094-b6fb-778612f024f9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_3f4f6e7b-6d8f-4cd4-a65a-4eeeb77bd847" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_e2c17745-dbb9-4600-97a5-ca2fe0974dae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_3f4f6e7b-6d8f-4cd4-a65a-4eeeb77bd847" xlink:to="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_e2c17745-dbb9-4600-97a5-ca2fe0974dae" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_7749347b-8e3d-4206-9160-af61d11508a3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_3f4f6e7b-6d8f-4cd4-a65a-4eeeb77bd847" xlink:to="loc_us-gaap_AccountsPayableCurrent_7749347b-8e3d-4206-9160-af61d11508a3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_1e50a147-292b-4a74-940f-e68942ad6f09" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_3f4f6e7b-6d8f-4cd4-a65a-4eeeb77bd847" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_1e50a147-292b-4a74-940f-e68942ad6f09" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_9f986dc1-09f1-41a1-98fa-d142942adfd2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_3f4f6e7b-6d8f-4cd4-a65a-4eeeb77bd847" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_9f986dc1-09f1-41a1-98fa-d142942adfd2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesAndOtherLiabilities_82f080de-5a25-4b70-8899-68b7dc1aa6b7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesAndOtherLiabilities"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_3f4f6e7b-6d8f-4cd4-a65a-4eeeb77bd847" xlink:to="loc_us-gaap_AccruedLiabilitiesAndOtherLiabilities_82f080de-5a25-4b70-8899-68b7dc1aa6b7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_c5c6ee83-a7c6-405e-b7a3-b2b60d993151" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_c5c6ee83-a7c6-405e-b7a3-b2b60d993151" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNoncurrent_b129ef39-b50d-40fa-9a45-bbc102ccd319" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:to="loc_us-gaap_InventoryNoncurrent_b129ef39-b50d-40fa-9a45-bbc102ccd319" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_98a96cc7-100d-4d2a-b953-5ffe2b64eb88" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:to="loc_us-gaap_AssetsCurrent_98a96cc7-100d-4d2a-b953-5ffe2b64eb88" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_c4de7fd9-21f4-4f2d-a3d9-eb3a8ce3e097" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_c4de7fd9-21f4-4f2d-a3d9-eb3a8ce3e097" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_90941c26-1b3b-424f-a7ff-cb11819f6e58" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_90941c26-1b3b-424f-a7ff-cb11819f6e58" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_PrepaidCommercialManufacturingNonCurrent_a69a8c15-cd16-44dc-978e-d0dd994cd51e" xlink:href="ardx-20250331.xsd#ardx_PrepaidCommercialManufacturingNonCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_47e5242c-8953-4ec9-8584-64cf36e0e939" xlink:to="loc_ardx_PrepaidCommercialManufacturingNonCurrent_a69a8c15-cd16-44dc-978e-d0dd994cd51e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryGross_38daf5d2-1e44-40c0-9b2d-c35adf351426" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:to="loc_us-gaap_InventoryGross_38daf5d2-1e44-40c0-9b2d-c35adf351426" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_PrepaidCommercialManufacturingCurrent_850c73f7-5223-4dd7-b450-9c4de0594045" xlink:href="ardx-20250331.xsd#ardx_PrepaidCommercialManufacturingCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:to="loc_ardx_PrepaidCommercialManufacturingCurrent_850c73f7-5223-4dd7-b450-9c4de0594045" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_0d2826c7-444f-4d45-bccc-420f5c6b4c79" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_0d2826c7-444f-4d45-bccc-420f5c6b4c79" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_0814a897-c827-4277-bae6-978c59a2e7ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_0814a897-c827-4277-bae6-978c59a2e7ec" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_4f6736c9-2921-4b29-8d99-5d151a927af4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_4f6736c9-2921-4b29-8d99-5d151a927af4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_02d1cd8d-6496-43c6-a73e-b41ac562cd4c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_240ba585-e55d-4325-a88b-63342aefbedc" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_02d1cd8d-6496-43c6-a73e-b41ac562cd4c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_45ba35a5-0b42-4fc1-94a3-f9740dd13e01" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_3f03a832-722f-4233-8c6a-b5bc558745e2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_45ba35a5-0b42-4fc1-94a3-f9740dd13e01" xlink:to="loc_us-gaap_CommonStockValue_3f03a832-722f-4233-8c6a-b5bc558745e2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalCommonStock_c12c8d8e-7b0a-4cfa-8d7b-b5f869f07ba7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapitalCommonStock"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_45ba35a5-0b42-4fc1-94a3-f9740dd13e01" xlink:to="loc_us-gaap_AdditionalPaidInCapitalCommonStock_c12c8d8e-7b0a-4cfa-8d7b-b5f869f07ba7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_6589cada-8fbe-4299-9812-8a14f07311b8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_45ba35a5-0b42-4fc1-94a3-f9740dd13e01" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_6589cada-8fbe-4299-9812-8a14f07311b8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_5dc144a0-027d-49ef-846b-e0481877f0b6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_45ba35a5-0b42-4fc1-94a3-f9740dd13e01" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_5dc144a0-027d-49ef-846b-e0481877f0b6" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/CONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="simple" xlink:href="ardx-20250331.xsd#CONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/CONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_d3e83e01-db6d-4cc9-9939-f6610e245be3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_f881947a-8946-424f-bcff-b1bc448cd6c9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_d3e83e01-db6d-4cc9-9939-f6610e245be3" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_f881947a-8946-424f-bcff-b1bc448cd6c9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_aef650dd-7239-4073-86ae-3ccf7e72ba45" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_d3e83e01-db6d-4cc9-9939-f6610e245be3" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_aef650dd-7239-4073-86ae-3ccf7e72ba45" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_855a67c8-0917-4849-b6ef-219632afdd07" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_5013f8a7-074f-48c3-8256-72deff41340a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_855a67c8-0917-4849-b6ef-219632afdd07" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_5013f8a7-074f-48c3-8256-72deff41340a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_c9bd46fc-a6a6-402f-b0fd-ad778d9252b4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_855a67c8-0917-4849-b6ef-219632afdd07" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_c9bd46fc-a6a6-402f-b0fd-ad778d9252b4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_dc5fb132-8983-4727-ae2f-348462b0a745" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_855a67c8-0917-4849-b6ef-219632afdd07" xlink:to="loc_us-gaap_CostsAndExpenses_dc5fb132-8983-4727-ae2f-348462b0a745" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_3b05decc-57fe-423d-a4fb-526c153afe3c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_8f79d214-b65f-4cfe-9289-6763fd36a14b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_3b05decc-57fe-423d-a4fb-526c153afe3c" xlink:to="loc_us-gaap_NetIncomeLoss_8f79d214-b65f-4cfe-9289-6763fd36a14b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_d0b64dc7-5860-49b6-b423-a8ed1b2d2bd2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_3b05decc-57fe-423d-a4fb-526c153afe3c" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_d0b64dc7-5860-49b6-b423-a8ed1b2d2bd2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_244c1546-84b0-4b0d-869d-bdd49095c0d2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_aa2d3deb-469c-486e-ae27-d79912d6a94b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_244c1546-84b0-4b0d-869d-bdd49095c0d2" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_aa2d3deb-469c-486e-ae27-d79912d6a94b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_46c08511-372a-4b49-a819-2de6a998c770" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_244c1546-84b0-4b0d-869d-bdd49095c0d2" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_46c08511-372a-4b49-a819-2de6a998c770" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3841d24f-c854-4d05-ac17-a2c189c247aa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_b425f7f4-0aa8-421b-adac-f1b6f64b01f8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3841d24f-c854-4d05-ac17-a2c189c247aa" xlink:to="loc_us-gaap_InterestExpenseNonoperating_b425f7f4-0aa8-421b-adac-f1b6f64b01f8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_76c29969-2c0d-4a6e-829c-1b1a56d205de" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3841d24f-c854-4d05-ac17-a2c189c247aa" xlink:to="loc_us-gaap_OperatingIncomeLoss_76c29969-2c0d-4a6e-829c-1b1a56d205de" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_4d7560fd-2a1a-44ae-b36e-a9c37f04e418" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3841d24f-c854-4d05-ac17-a2c189c247aa" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_4d7560fd-2a1a-44ae-b36e-a9c37f04e418" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_NonCashInterestExpenseRelatedToSaleOfRoyalties_e918971a-2250-4d4d-b442-b0373f378ae0" xlink:href="ardx-20250331.xsd#ardx_NonCashInterestExpenseRelatedToSaleOfRoyalties"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_3841d24f-c854-4d05-ac17-a2c189c247aa" xlink:to="loc_ardx_NonCashInterestExpenseRelatedToSaleOfRoyalties_e918971a-2250-4d4d-b442-b0373f378ae0" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/CONDENSEDSTATEMENTSOFCASHFLOWS" xlink:type="simple" xlink:href="ardx-20250331.xsd#CONDENSEDSTATEMENTSOFCASHFLOWS"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/CONDENSEDSTATEMENTSOFCASHFLOWS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_3c2a4871-e224-4ec0-99c1-4c1f2969fb2d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_0946d1ae-b5f2-420d-a9ac-609e916a81e3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_3c2a4871-e224-4ec0-99c1-4c1f2969fb2d" xlink:to="loc_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_0946d1ae-b5f2-420d-a9ac-609e916a81e3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_f88d7665-97d4-4843-bae4-eb44e5b17380" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_3c2a4871-e224-4ec0-99c1-4c1f2969fb2d" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_f88d7665-97d4-4843-bae4-eb44e5b17380" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireShortTermInvestments_0f029dd4-e8cd-4ace-b166-8eb23c3c0587" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireShortTermInvestments"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_3c2a4871-e224-4ec0-99c1-4c1f2969fb2d" xlink:to="loc_us-gaap_PaymentsToAcquireShortTermInvestments_0f029dd4-e8cd-4ace-b166-8eb23c3c0587" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_5e725139-fbbe-4534-92fc-85dc3c180480" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_3cd307e9-8799-4a09-87b7-22996eaa7739" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_5e725139-fbbe-4534-92fc-85dc3c180480" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_3cd307e9-8799-4a09-87b7-22996eaa7739" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfSecuredDebt_75dd3fb3-4fc6-40dc-b607-436b7804d37c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfSecuredDebt"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_5e725139-fbbe-4534-92fc-85dc3c180480" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfSecuredDebt_75dd3fb3-4fc6-40dc-b607-436b7804d37c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_5b37b854-2bdd-42fe-8800-f032b5ed8412" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_5b37b854-2bdd-42fe-8800-f032b5ed8412" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_c57f6722-e51c-4aa9-9791-939f2718780f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_c57f6722-e51c-4aa9-9791-939f2718780f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities_4f70f32f-01c1-4418-b17e-715a22c77d6a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities_4f70f32f-01c1-4418-b17e-715a22c77d6a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_51b096cc-ace2-4530-9e48-51ebc1180062" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_NetIncomeLoss_51b096cc-ace2-4530-9e48-51ebc1180062" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_1ce568ce-4873-4cf2-a55b-f6354a553177" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherOperatingActivitiesCashFlowStatement"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_1ce568ce-4873-4cf2-a55b-f6354a553177" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInInventories_91a8a5cc-defd-4954-bcf0-1f2c7d3bbdef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInInventories"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInInventories_91a8a5cc-defd-4954-bcf0-1f2c7d3bbdef" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_4fe06230-9929-46b5-a85f-cf9e5f3f7e53" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_ShareBasedCompensation_4fe06230-9929-46b5-a85f-cf9e5f3f7e53" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_779309fe-717c-45cb-bcc5-291be1b90be3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_779309fe-717c-45cb-bcc5-291be1b90be3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfDebtDiscountPremium_86e60943-8b0d-46c0-a589-80e01246d373" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AmortizationOfDebtDiscountPremium"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_AmortizationOfDebtDiscountPremium_86e60943-8b0d-46c0-a589-80e01246d373" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_IncreaseDecreaseInPrepaidCommercialManufacturingExpense_25acee7a-05f0-4eed-bab4-c29a9d0d3466" xlink:href="ardx-20250331.xsd#ardx_IncreaseDecreaseInPrepaidCommercialManufacturingExpense"/>
    <link:calculationArc order="10" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_ardx_IncreaseDecreaseInPrepaidCommercialManufacturingExpense_25acee7a-05f0-4eed-bab4-c29a9d0d3466" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInEmployeeRelatedLiabilities_28fbcff2-f83a-4713-8ad3-5ae6664f8330" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInEmployeeRelatedLiabilities"/>
    <link:calculationArc order="11" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInEmployeeRelatedLiabilities_28fbcff2-f83a-4713-8ad3-5ae6664f8330" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_a25f8071-aa2e-43b5-a764-ab720b6ac493" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="12" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_a25f8071-aa2e-43b5-a764-ab720b6ac493" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOperatingLeaseLiability_358bcf54-97d8-4b15-a766-d04dd37208c3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInOperatingLeaseLiability"/>
    <link:calculationArc order="13" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInOperatingLeaseLiability_358bcf54-97d8-4b15-a766-d04dd37208c3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInDeferredRevenue_34b84820-d75b-4115-80ad-3cc445a459aa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInDeferredRevenue"/>
    <link:calculationArc order="14" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInDeferredRevenue_34b84820-d75b-4115-80ad-3cc445a459aa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_8b1457e8-36eb-4cf2-aae8-b4c72723e566" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="15" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_8b1457e8-36eb-4cf2-aae8-b4c72723e566" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_NonCashRoyaltyRelatedToSaleOfFutureRoyalties_d14dd3d1-a900-4b25-a008-b747bbf2cc66" xlink:href="ardx-20250331.xsd#ardx_NonCashRoyaltyRelatedToSaleOfFutureRoyalties"/>
    <link:calculationArc order="16" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c60c21c0-7f2c-443d-a04b-e3a01682a051" xlink:to="loc_ardx_NonCashRoyaltyRelatedToSaleOfFutureRoyalties_d14dd3d1-a900-4b25-a008-b747bbf2cc66" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_7ed4d70f-ffe3-4c12-9262-ca5c227446f1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_de6f1abe-1b43-495a-84d7-9c8f677cb81d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_7ed4d70f-ffe3-4c12-9262-ca5c227446f1" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_de6f1abe-1b43-495a-84d7-9c8f677cb81d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_46cc4874-b649-4a6a-b1ce-47ea4bacc850" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_7ed4d70f-ffe3-4c12-9262-ca5c227446f1" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_46cc4874-b649-4a6a-b1ce-47ea4bacc850" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_e213ad72-aa83-49c2-aa2a-4e2cdebdddf0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_7ed4d70f-ffe3-4c12-9262-ca5c227446f1" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_e213ad72-aa83-49c2-aa2a-4e2cdebdddf0" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/CASHCASHEQUIVALENTSANDSHORTTERMINVESTMENTSSecuritiesClassifiedasCashCashEquivalentsandInvestmentsDetails" xlink:type="simple" xlink:href="ardx-20250331.xsd#CASHCASHEQUIVALENTSANDSHORTTERMINVESTMENTSSecuritiesClassifiedasCashCashEquivalentsandInvestmentsDetails"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/CASHCASHEQUIVALENTSANDSHORTTERMINVESTMENTSSecuritiesClassifiedasCashCashEquivalentsandInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ardx_InvestmentsAndCashAmortizedCost_66fff5bf-fd8d-4429-8bef-9e9e70ec1cea" xlink:href="ardx-20250331.xsd#ardx_InvestmentsAndCashAmortizedCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_7263f94d-7826-47ad-955a-9e4db4263f39" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_InvestmentsAndCashAmortizedCost_66fff5bf-fd8d-4429-8bef-9e9e70ec1cea" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_7263f94d-7826-47ad-955a-9e4db4263f39" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_1d25153e-3037-4742-971e-44d4644bbcf1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_InvestmentsAndCashAmortizedCost_66fff5bf-fd8d-4429-8bef-9e9e70ec1cea" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_1d25153e-3037-4742-971e-44d4644bbcf1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_04cd37ad-dd15-4715-9fca-d1e3b3598717" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_892fa5ae-ab57-43ee-a436-d85759da0947" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_04cd37ad-dd15-4715-9fca-d1e3b3598717" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_892fa5ae-ab57-43ee-a436-d85759da0947" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_6b781c06-a844-47dc-b982-1d18c8f5e657" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_04cd37ad-dd15-4715-9fca-d1e3b3598717" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_6b781c06-a844-47dc-b982-1d18c8f5e657" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_e4b977ca-9815-4537-9c76-d78e8f2fbaac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_04cd37ad-dd15-4715-9fca-d1e3b3598717" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_e4b977ca-9815-4537-9c76-d78e8f2fbaac" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsAndCash_e6e2a3b2-c11f-45b1-9855-4f9315ee0dfc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentsAndCash"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_52182df9-6256-42b5-895b-6619bd02c7f8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InvestmentsAndCash_e6e2a3b2-c11f-45b1-9855-4f9315ee0dfc" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_52182df9-6256-42b5-895b-6619bd02c7f8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_315d6926-2a66-41d0-9120-8a75bff13743" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InvestmentsAndCash_e6e2a3b2-c11f-45b1-9855-4f9315ee0dfc" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_315d6926-2a66-41d0-9120-8a75bff13743" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedLosses_6a86e539-37c6-4050-9b37-c508912cad23" xlink:href="ardx-20250331.xsd#ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedLosses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_87fa41fc-514c-428c-810c-b89924aa4b59" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedLosses_6a86e539-37c6-4050-9b37-c508912cad23" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_87fa41fc-514c-428c-810c-b89924aa4b59" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedGains_172430c9-bd14-4a11-9e7d-9f225bf7eaf9" xlink:href="ardx-20250331.xsd#ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedGains"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_a9bf2d00-1801-49b1-95eb-74d6b66ddecb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedGains_172430c9-bd14-4a11-9e7d-9f225bf7eaf9" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_a9bf2d00-1801-49b1-95eb-74d6b66ddecb" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/CASHCASHEQUIVALENTSANDSHORTTERMINVESTMENTSSecuritiesClassifiedasCashCashEquivalentsandInvestmentsDetails_1" xlink:type="simple" xlink:href="ardx-20250331.xsd#CASHCASHEQUIVALENTSANDSHORTTERMINVESTMENTSSecuritiesClassifiedasCashCashEquivalentsandInvestmentsDetails_1"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/CASHCASHEQUIVALENTSANDSHORTTERMINVESTMENTSSecuritiesClassifiedasCashCashEquivalentsandInvestmentsDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ardx_InvestmentsAndCashAmortizedCost_828416a0-6240-4907-997a-44ded8dcc579" xlink:href="ardx-20250331.xsd#ardx_InvestmentsAndCashAmortizedCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedLosses_acc79356-c12f-4705-b2bd-ecaa932e0801" xlink:href="ardx-20250331.xsd#ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedLosses"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_InvestmentsAndCashAmortizedCost_828416a0-6240-4907-997a-44ded8dcc579" xlink:to="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedLosses_acc79356-c12f-4705-b2bd-ecaa932e0801" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsAndCash_de1823e4-c31c-4490-bddb-02aee429731d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentsAndCash"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_InvestmentsAndCashAmortizedCost_828416a0-6240-4907-997a-44ded8dcc579" xlink:to="loc_us-gaap_InvestmentsAndCash_de1823e4-c31c-4490-bddb-02aee429731d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedGains_09df39d9-ca85-436a-8324-5968e2e9427e" xlink:href="ardx-20250331.xsd#ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedGains"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_ardx_InvestmentsAndCashAmortizedCost_828416a0-6240-4907-997a-44ded8dcc579" xlink:to="loc_ardx_CashCashEquivalentsAndInvestmentsGrossUnrealizedGains_09df39d9-ca85-436a-8324-5968e2e9427e" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/INVENTORYScheduleofInventoryDetails" xlink:type="simple" xlink:href="ardx-20250331.xsd#INVENTORYScheduleofInventoryDetails"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/INVENTORYScheduleofInventoryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_1d1eba1e-0fc1-41bd-9f03-61f9d7d67e48" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoods_e48636df-2b70-404a-bf19-b5fae33a8ad3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryFinishedGoods"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_1d1eba1e-0fc1-41bd-9f03-61f9d7d67e48" xlink:to="loc_us-gaap_InventoryFinishedGoods_e48636df-2b70-404a-bf19-b5fae33a8ad3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryRawMaterials_3cfed656-7f4d-43b3-952d-33d9a6b1438e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryRawMaterials"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_1d1eba1e-0fc1-41bd-9f03-61f9d7d67e48" xlink:to="loc_us-gaap_InventoryRawMaterials_3cfed656-7f4d-43b3-952d-33d9a6b1438e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWorkInProcess_3c5b5c8f-05f2-48a7-b150-6dd9d0734464" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryWorkInProcess"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_1d1eba1e-0fc1-41bd-9f03-61f9d7d67e48" xlink:to="loc_us-gaap_InventoryWorkInProcess_3c5b5c8f-05f2-48a7-b150-6dd9d0734464" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/INVENTORYScheduleofInventoryDetails_1" xlink:type="simple" xlink:href="ardx-20250331.xsd#INVENTORYScheduleofInventoryDetails_1"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/INVENTORYScheduleofInventoryDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_5c5b23c3-12ba-411c-a372-b4b77c7b1614" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryGross_21160121-a6eb-4c85-9ff0-e386faa81af0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_5c5b23c3-12ba-411c-a372-b4b77c7b1614" xlink:to="loc_us-gaap_InventoryGross_21160121-a6eb-4c85-9ff0-e386faa81af0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNoncurrent_b8b97127-47a7-44b5-9fda-545f67df904d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_5c5b23c3-12ba-411c-a372-b4b77c7b1614" xlink:to="loc_us-gaap_InventoryNoncurrent_b8b97127-47a7-44b5-9fda-545f67df904d" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/BORROWINGScheduleofBorrowingsDetails" xlink:type="simple" xlink:href="ardx-20250331.xsd#BORROWINGScheduleofBorrowingsDetails"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/BORROWINGScheduleofBorrowingsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_86135385-32ed-4e5e-8890-7417228e98c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebt"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_bb7a58d5-a589-410b-8234-8d8e74a48342" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_86135385-32ed-4e5e-8890-7417228e98c1" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_bb7a58d5-a589-410b-8234-8d8e74a48342" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFeeAmount_d2c6141a-5204-4ba5-b76f-c3c131a444f3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFeeAmount"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_86135385-32ed-4e5e-8890-7417228e98c1" xlink:to="loc_us-gaap_DebtInstrumentFeeAmount_d2c6141a-5204-4ba5-b76f-c3c131a444f3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_41cdc9f5-96cb-4117-9278-8262793c6cdf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_86135385-32ed-4e5e-8890-7417228e98c1" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_41cdc9f5-96cb-4117-9278-8262793c6cdf" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/BORROWINGScheduleofBorrowingsDetails_1" xlink:type="simple" xlink:href="ardx-20250331.xsd#BORROWINGScheduleofBorrowingsDetails_1"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/BORROWINGScheduleofBorrowingsDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_d0a523bc-c711-4671-9563-2f2dd85c5b94" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebt"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LoansPayableCurrent_4d9b57f2-1e84-4fa5-8912-9323625504b2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LoansPayableCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_d0a523bc-c711-4671-9563-2f2dd85c5b94" xlink:to="loc_us-gaap_LoansPayableCurrent_4d9b57f2-1e84-4fa5-8912-9323625504b2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermLoansPayable_17eb9c5f-c768-4e3b-bbe3-7d37e3f4cb5b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermLoansPayable"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_d0a523bc-c711-4671-9563-2f2dd85c5b94" xlink:to="loc_us-gaap_LongTermLoansPayable_17eb9c5f-c768-4e3b-bbe3-7d37e3f4cb5b" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/LEASESAdditionalDetailsofLeasesDetails" xlink:type="simple" xlink:href="ardx-20250331.xsd#LEASESAdditionalDetailsofLeasesDetails"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/LEASESAdditionalDetailsofLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_6236b375-6aa4-4682-9611-5b63a9e49ab0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_ed68ee6c-b853-441e-8ec3-fbb23ce49b11" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_6236b375-6aa4-4682-9611-5b63a9e49ab0" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_ed68ee6c-b853-441e-8ec3-fbb23ce49b11" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_e1c41935-22c4-4a1b-be35-23602145965a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_6236b375-6aa4-4682-9611-5b63a9e49ab0" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_e1c41935-22c4-4a1b-be35-23602145965a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/LEASESUndiscountedCashPaymentObligationsforOperatingLeaseLiabilitiesDetails" xlink:type="simple" xlink:href="ardx-20250331.xsd#LEASESUndiscountedCashPaymentObligationsforOperatingLeaseLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/LEASESUndiscountedCashPaymentObligationsforOperatingLeaseLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_edd631cb-e85b-4e17-a53b-7b2085a61610" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_8eb72cec-da0f-4688-b7d8-db4e05eb2114" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_edd631cb-e85b-4e17-a53b-7b2085a61610" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_8eb72cec-da0f-4688-b7d8-db4e05eb2114" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_01c3d34f-bf9d-4be8-aa07-cf548f81f23a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_edd631cb-e85b-4e17-a53b-7b2085a61610" xlink:to="loc_us-gaap_OperatingLeaseLiability_01c3d34f-bf9d-4be8-aa07-cf548f81f23a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/LEASESUndiscountedCashPaymentObligationsforOperatingLeaseLiabilitiesDetails_1" xlink:type="simple" xlink:href="ardx-20250331.xsd#LEASESUndiscountedCashPaymentObligationsforOperatingLeaseLiabilitiesDetails_1"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/LEASESUndiscountedCashPaymentObligationsforOperatingLeaseLiabilitiesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_322e3138-bdb1-41fa-ab93-d23acecdf914" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_322e3138-bdb1-41fa-ab93-d23acecdf914" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_9280a0a9-f614-486a-87d7-a6845ec5c40a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_9280a0a9-f614-486a-87d7-a6845ec5c40a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_6f335814-7c8a-40a3-965b-6027a65ed97f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_6f335814-7c8a-40a3-965b-6027a65ed97f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour_8e668242-ce9e-4b63-8f60-ec142ec4b601" xlink:href="ardx-20250331.xsd#ardx_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:to="loc_ardx_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour_8e668242-ce9e-4b63-8f60-ec142ec4b601" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_60bf142b-8c2c-4cc1-a44e-4ad7ebf35a8a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_60bf142b-8c2c-4cc1-a44e-4ad7ebf35a8a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_412ccea5-5e5a-4c5a-8d09-00ba3ce92ba1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_964b6214-52e4-4f68-b7eb-fb6ac99acf54" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_412ccea5-5e5a-4c5a-8d09-00ba3ce92ba1" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ardelyx.com/role/SEGMENTREPORTINGScheduleofOperatingSegmentDetails" xlink:type="simple" xlink:href="ardx-20250331.xsd#SEGMENTREPORTINGScheduleofOperatingSegmentDetails"/>
  <link:calculationLink xlink:role="http://www.ardelyx.com/role/SEGMENTREPORTINGScheduleofOperatingSegmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_82fe5813-c9ff-4144-89b4-0974fd9b680e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_SegmentReportingOtherReconcilingItemAmount_41b35daf-7002-4250-bb23-d99b09507323" xlink:href="ardx-20250331.xsd#ardx_SegmentReportingOtherReconcilingItemAmount"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_82fe5813-c9ff-4144-89b4-0974fd9b680e" xlink:to="loc_ardx_SegmentReportingOtherReconcilingItemAmount_41b35daf-7002-4250-bb23-d99b09507323" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_b4584b7d-099a-49fa-a9e7-0d5f775e069e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_82fe5813-c9ff-4144-89b4-0974fd9b680e" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_b4584b7d-099a-49fa-a9e7-0d5f775e069e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_ecd2bb7a-52a6-4fb2-becd-9a975237a26b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_ResearchAndDevelopmentExpenseAdjusted_5154efe8-2883-4826-9e46-d2294d71ff15" xlink:href="ardx-20250331.xsd#ardx_ResearchAndDevelopmentExpenseAdjusted"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ecd2bb7a-52a6-4fb2-becd-9a975237a26b" xlink:to="loc_ardx_ResearchAndDevelopmentExpenseAdjusted_5154efe8-2883-4826-9e46-d2294d71ff15" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_ardx_ShareBasedPaymentArrangementExpenseAdjusted_18bad1e4-106d-4a53-b2b7-8bc941a439ac" xlink:href="ardx-20250331.xsd#ardx_ShareBasedPaymentArrangementExpenseAdjusted"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ecd2bb7a-52a6-4fb2-becd-9a975237a26b" xlink:to="loc_ardx_ShareBasedPaymentArrangementExpenseAdjusted_18bad1e4-106d-4a53-b2b7-8bc941a439ac" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingExpense_632ac962-b377-497f-a874-144858833355" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ecd2bb7a-52a6-4fb2-becd-9a975237a26b" xlink:to="loc_us-gaap_SellingExpense_632ac962-b377-497f-a874-144858833355" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_aadf4854-a455-48ef-9f5c-fbe2e7195c57" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ecd2bb7a-52a6-4fb2-becd-9a975237a26b" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_aadf4854-a455-48ef-9f5c-fbe2e7195c57" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_e64c8b64-03a3-4d72-a8b4-1b27f97ca4b4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ecd2bb7a-52a6-4fb2-becd-9a975237a26b" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_e64c8b64-03a3-4d72-a8b4-1b27f97ca4b4" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
