The present study was conducted to evaluate the cardioprotective role of a medicinal mushroom, Ganoderma lucidum against the toxicity of an anticancer drug adriamycin. Wistar rats were administered with adriamycin (1.5 mg kg-1 b.wt.) for three weeks to induce cardiotoxicity. Another group was treated with adriamycin and Ganoderma extract (250 mg kg-1) for 30 days. Adriamycin treatment resulted in increased serum levels of marker enzymes such as alanine amino transferase (ALT), aspartate amino transferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK). Besides increasing the lipid peroxidation (LPO), adriamycin significantly reduced antioxidant enzymes, glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in the heart tissue. Level of reduced glutathione (GSH) was also significantly reduced. However, in G. lucidum extract treated rats the alterations were not significant, but found to be nearer to the control. The study shows that G. lucidum extract exhibits significant antioxidant property and protect the heart from free radical mediated toxicity of adriamycin.