Introduction: Cisplatin interacts with DNA and induces an immunological response and reactive oxygen species, which are nephrotoxic mediators. Stem cells self-renew through symmetric divisions and can develop into other cell types due to their multipotency. Dexpanthenol has been proven to protect against renal injury. Aim: This study aims to demonstrate that dexpanthenol could improve the effect of adipose-derived mesenchymal stem cells (ADMSC) against cisplatin-induced acute kidney injury. Methods: Sixty male Sprague-Dawley rats were divided into 5 groups (N = 12): control, cisplatin, cisplatin & dexpanthenol, cisplatin & ADMSC, and cisplatin & dexpanthenol & ADMSCs. On the 5th day following cisplatin injection, half the rats in each group were sacrificed, and the other half were sacrificed on the 12th day. Histopathological examination, molecular studies (IL-6, Bcl2, TGFb-1, Caspase-3, Fibronectin, and b-catenin), antioxidants (superoxide dismutase and catalase), and renal function were all investi- gated. Results: In contrast to cisplatin group, the dexpanthenol and ADMSCs treatments significantly decreased renal function and oxidative stress while significantly enhancing antioxidants. Dexpanthenol improved stem cells by significantly down-regulating caspase-3, IL-6, TGF-b1, Fibronectin, and b-catenin and signif- icantly up-regulating Bcl2 and CD34, which reversed the cisplatin effect. Conclusion: Dexpanthenol enhanced ADMSCs’ ability to protect against cisplatin-induced AKI by decreas- ing inflammation, apoptosis, and fibrosis. Ó 2023 The Author(s). Published by Elsevier B.V.