The protective effect of an ethanol extract of Curcuma comosa against cisplatin-induced renal toxicity in mice was studied. Adult male mice were pretreated for 4 days with the ethanol extract of C. comosa [100-200 mg/kg body weight (BW), orally (p.o.)] before injection of cisplatin (12.5 mg/kg BW, intraperitoneally (i.p.)). Five days later the mice were killed, and blood samples were collected to determine blood urea nitrogen (BUN) and plasma creatinine levels. Kidneys were examined histopathologically and levels of lipid peroxidation, gluthathione (GSH) content, and superoxide dismutase (SOD), gluthathione peroxidase (GPx), and catalase (CAT) activities were determined. Histological examinations revealed degenerative changes and tubular necrosis in mice treated with cisplatin, which were improved by pretreatment with C. comosa ethanol extract. Cisplatin raised BUN, creatinine, and kidney lipid peroxidation levels, and lowered kidney GSH content and levels of GPx, SOD, and CAT activities, all of which (except SOD and CAT) could be restored to normal values by pretreatment with 200 mg/kg BW of C. comosa ethanol extract. In addition, the ethanol extract of C. comosa and its isolated diarylheptanoid compound also exhibited radical scavenging activities. The results suggest that the ethanol extract of C. comosa exhibits effective protection against cisplatin-induced nephrotoxicity mediated through its antioxidant activity.