Doxorubicin is a powerful anticancer antibiotic extensively used in the treatment of several typesof cancers. Long-term administration of this drug results in cumulative dose related cardiotoxicity dueto enhanced production of free radicals leading to oxidative stress. Our earlier investigations havedemonstrated significant antioxidant, anti-inflammatory and antitumour properties of Ganodermalucidum extracts. We extended our investigations to evaluate the protective effect of Ganodermalucidum extract against doxorubicin-induced cardiotoxicity. Administration of 3 doses of doxorubicin,6 mg/kg body weights, i.p. per each dose, alternative days, showed clear signs of cardiotoxicity inrats. The drug enhanced serum creatine kinase (CK) activity and lipid peroxidation in tissuedrastically. The drug also induced significant decrease in GSH level and activities of CAT, SODand GPx. Administration of methanolic extract of G.lucidum (500 and 1,000 mg/kg body weight)significantly increased the level of GSH and activities of CAT, SOD and GPx. Activity of CK wassignificantly lowered in a dose dependent manner. The treatment also caused significant decreasein lipid peroxidation (MDA). The results thus indicated that methanolic extract of G.lucidumprevented oxidative stress caused by doxorubicin administration and the increase in serum CKactivity and lipid peroxidation in the tissue. The experimental findings suggest the therapeuticpotential of G.lucidum as adjuvant in cancer chemotherapy.