Background: Traditionally, Berberis lyceum was extensively used for the treatment of several human diseases. Objective: This study was undertaken to determine in vivo effects of Berberis lyceum root bark against doxorubicin-induced cardiotoxicity and cisplatin-induced neurotoxicity in Sprague Dawley rats. Methods: A single dose of doxorubicin (20 mg/ kg i. p) and cisplatin (4mg/kg i.p) was used to induce cardiotoxicity and neurotoxicity, respectively. Berberis lyceum methanolic extract was given orally (200 and 400 mg/ kg) to toxicity-induced rats. The cardiac biomarkers i.e. serum aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, creatine kinase and creatine kinase MB were analyzed in blood collected from cardiotoxic rats. The tissue oxidative stress markers included protein, glutathione s-transferase specific activity, catalase activity, total glutathione, and malondialdehyde levels were measured in cardiac and brain homogenate of the respective groups. Results: Berberis lyceum methanolic extract has the potential to reduce the doxorubicin-induced cardiotoxicity and cisplatin-induced neurotoxicity significantly (*p<0.05) by reducing the serum markers and oxidative stress parameters. Histopathological analysis exhibited a marked improvement in the morphology of cardiac and brain tissues. Conclusion: It is concluded that methanolic extract of Berberis lyceum root bark has the potential to protect and reverse anticancer drugs induced cardiotoxicity and neurotoxicity. Keywords: Doxorubicin; Cisplatin; Berberis lyceum; Cardiotoxicity; Neurotoxicity; Antioxidant.