Cisplatin (CP) is one of the most frequently used chemotherapy agents. The objective of this design was to determine the ameliorative effect of lycopene (LP) and/or N-acetylcysteine (NAC) in rats with hepatic and renal toxicity induced by CP. Rats were divided randomly into 7 groups (7 rats/group): control vehicle group (saline only), the LP group (10 mg/kg, orally), the NAC group (150 mg/kg, orally), the CP group (7.5 mg/kg, IP on day 27), the LP-CP group, the NAC-CP group, and the LP-NAC-CP group. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (APK) and levels of urea, creatinine, and lipids (cholesterol, triglycerides, and low-density lipoprotein-cholesterol) increased after CP injection in the serum. Moreover, CP decreased levels of protein, albumin, and HDL-cholesterol. Meanwhile, malondialdehyde significantly increased with a decrease in reduced glutathione, superoxide dismutase, and catalase in the liver and kidney tissues. CP also induced some pathological lesions and increased the expression of caspase-3 in the liver and kidney tissues. Administration of LP and NAC alone or in combinations ameliorated hepatorenal toxicity and apoptosis induced by CP.