Background: Cisplatin chemotherapy induces nephrotoxicity by producing reactive oxygen species, hence, discovering add-on nephroprotective drugs for patients with cancer is challenging. Boesenbergia rotunda has been reported for its antioxidant properties. Purpose: This study aims to explore the nephroprotective mechanism of the ethanol extract of Boesenbergia rotunda rhizome (EEBR) in cisplatin-induced rats. Methods: The rats were randomly assigned into 6 groups: the normal control (treated with saline); the negative control (cisplatininduced without any treatment); the positive control (treated with quercetin 50 mg/kg BW); and 3 treatment EEBR (125 mg/kg BW; 250 mg/kg BW; 500 mg/kg BW) groups for 10 days. The % relative organ weight, kidney histopathology, and nephrotoxicity biomarkers expression were evaluated. Results: EEBR decreased creatinine, urea nitrogen, glutamic pyruvate transaminase, and malondialdehyde levels in the blood of cisplatin-induced rats. An insignificant increase in GOT was observed in rats treated with the highest dose of EEBR. EEBR did not significantly alter the BW and the % kidney relative weight. An abnormal shape of the Bowman capsule is observed in the negative control group. EEBR reduced the expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 genes in rats' kidneys. Conclusion: Boesenbergia rotunda could be considered a potential candidate for add-on therapy in cisplatin-treated patients, but further studies are needed to verify its efficacy and safety.