Physalis peruviana has been widely used as a medicinal herb for treating various diseases since ancient times. This study aimed to examine the hepatoprotective potential of the ethanolic extract of P. peruviana fruit (EPPF) against lead acetate (LA) intoxicated male albino rats. The experimental rats were divided into ten groups of 4 animals. Animal of Group I served as normal, Group II animals were administered orally 15 mg/Kg body weight of LA, Group III to V animals received EPPF 150mg/kg, 300 mg/kg and 600 mg/kg respectively, Group VI animals received standard silymarin 50 mg/kg, and Group VII to X were treated with LA (15 mg/kg) with EPPF 150, 300, 600 and std 50 mg/kg, orally for 32 days respectively. The degree of protection was measured by estimating hematological parameters such as Hb, RBC, WBC, PCV, platelets, MCV, MCHC, and ESR and biochemical parameters such as urea, creatinine, Cholesterol, HDL, LDL, VLDL, bilirubin, SGOT, SGBT, ALP, GGT, protein, albumin and globulin. Lead acetate induced alterations of hematological and biochemical parameters were observed in group II animals and these levels brought back to normal in the animals treated with EPPF at the concentrations of 150, 300 and 600 mg/kg which was significantly similar to silymarin treated animals. The data of the results obtained depicted that the fruit extract of P. peruviana was found to have promising protective efficacy against lead acetate induced liver toxicity.