Punica granatum Linn popularly known as ‘Pomegranate’ is a rich source of flavonoids. Flavonoids have been implicated in Hepatoprotective activity. Objectives: To evaluate effect of Punica granatum seeds and its flavonoids on doxorubicin-induced hepatotoxicity in Wistar rats. Materials and Methods: The Anthocyanidins of Punica granatum (100 mg/kg) extracts as potent antioxidants in improving the toxicity of doxorubicin (DOX) and/or gamma radiation in albino Wistar rats. The rats were injected with DOX (2.5 mg/kg, i.p.) and/or exposed the rats to irradiation (2 Gy, whole body) weekly, for four consecutive weeks. The antioxidant treatments were used daily via oral gavages for two weeks protection period and during the experiment (4 weeks). The levels of aminotranferases (ASAT, ALAT), alkaline phosphatase (ALP) and Superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GSH) and Lipid peroxidation (TBARS) levels in liver were measured. Result: In the present study, DOX and/or gamma radiation revealed increase in the hepatic biomarkers (ASAT, ALAT and ALP), also decreased in total protein and albumin, which were significantly decreased after pretreatment with Pomegranate (POM) (100 mg/kg), while decreased in total protein and albumin. DOX and/or gamma radiation significantly decreased levels of SOD, CAT, and GSH which were restored with POM. Conclusion: The study concludes that POM possess potential hepatoprotective activity which may be attributated to its flavonoids (anthocyanidins), having therapeutic potential in treatment of liver disorders.