This study aims to investigate the role of oxidants in cisplatin-induced nephrotoxicity. Cisplatin was administered intraperitoneally (i.p.) in a single dose (5mg/kg) and guinea pigs were killed either after 24h or 7 days. The same experiment was performed using animals treated with vitamins C and E combination and a natural antioxidant extract (SARMEX((R))). The kidneys were then removed to be used in the analyses. Blood samples were also obtained from the animals to be used in routine biochemical assays. Twenty-four hours after treatment there was a significant decrease in the renal activities of total superoxide scavenger activity (TSSA), superoxide dismutase (SOD) and catalase (CAT) accompanied by a rise in malondialdehyde (MDA) levels. After 7 days, the fall in kidney enzymatic activities was far greater, while the increase in blood urea (BUN) and creatinine (CRE) was marked. Treatment with antioxidants causes significant increases in renal TSSA (7 day), non-enzymatic superoxide scavenger activity (NSSA) (24h and 7 day) and SOD (7 day) activities, does not change glutathione peroxidase (GSH-Px) activity and decreases renal MDA (24h and 7 day), blood BUN (7 day) and CRE (7 day) levels. Our results suggest that cisplatin treatment impairs both enzymatic and non-enzymatic antioxidant systems and causes peroxidation in the renal tissue, which leads to kidney failure. Antioxidant supplementation strengthens the renal antioxidant system, eliminates oxidation reactions, and prevents cisplatin-induced kidney failure.