Background: Despite being efficient anti-neoplastic agent, Cisplatin therapy leads to nephrotoxicity as a major associated complication implicated to be induced via oxidative stress. Aim of the Work: This study was conducted to compare the nephro-protective effects of vitamin-C or L-carnitine in amelioration of the dramatic toxic effects of Cisplatin on renal tissue. Material and Methods: A total of thirty male mice were divided into six groups; each included 5 mice. Group (I) used as the control, mice received a single intraperitoneal (IP) injection of 1.5 ml of sterile distilled water. Group (II) is treated mice with a single IP injection of Cisplatin (10 mg/kg BW). In group (III) the animals received Cisplatin as in group II plus ascorbic acid (500 mg/kg BW) orally for 2 days before and 3days after Cisplatin injection. Group (IV) is L-carnitine +Cisplatin-treated mice, received Cisplatin as in group II plus L-carnitine (200 mg/kg BW) orally for 2 days before and 3days after Cisplatin injection. Group (V) is Ascorbic acid-treated animals that received the same dose of ascorbic acid as in group III orally for 5 consecutive days. Group (VI) is L-carnitine-treated animals, which received the same dose of L-carnitine as in group IV orally for consecutive 5 days. Results: Mice treated with Cisplatin showed extensive tubular necrosis, presence of casts in the cortex, changes in the basement membrane and brush border loss. While, mice treated with both Cisplatin and vitamin C or L-carnitine revealed marked reduction in the apoptotic cells, maintenance of brush border and marked decrease in basement membrane oedema.  Conclusions: L- carnitine supply is a better protection against the nephrotoxic effects of drug Cisplatin.