Cisplatin (cis-diamminedichloroplatinum II) is one of the most effective chemotherapeutic agents used in the treatment of a variety of human solid tumors. However, its clinical use is limited due to severe toxicity. The pathogenesis of liver damage caused by cisplatin is generally considered to be oxidative damage. The aim of this study was to evaluate the protective effect of the ethanol extract of Prunus persica flesh (PPFE) against cisplatin-induced hepatotoxicity in animal models. In a xenograft model with the repeated administration of a low-dose cisplatin (5 mg/kg body weight) for 15 days, and in an acute toxicity model with a single administration of a high-dose cisplatin (45 mg/kg body weight) over a 16 h period, the consecutive administration of PPFE in combination with and prior to the cisplatin injection reversed the cisplatin-induced decrease in the liver weight as a percentage of total body weight, and the cisplatin-induced increases in the serum alanine aminotransferase and aspartate aminotransferase levels caused by liver damage. Moreover, the oral administration of PPFE significantly recovered the reduced glutathione level and inhibited lipid peroxidation in the cisplatin-treated mice. These results demonstrate that supplementation with PPFE might protect against cisplatin-induced toxicity in cancer patients.