Abstract: The current communication was designed to assess the cardioprotective effect of the methanolic leaf extract of Ficus hispida Linn. (FH) (400 mg kg-1 body weight, administered orally for 10 days) on cyclophosphamide (CP) provoked oxidative injury in rat heart. CP cardiotoxicity, induced by single intraperitoneal injection (200 mg kg-1 b.wt.), was revealed by elevated serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT). CP induced rats, treated with FH depicted near normalcy in these parameters. In the CP group, increased oxidative stress was evidenced by a significant rise in myocardial malondialdehyde (MDA) level and decline in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and reduced glutathione (GSH) activities in the heart tissue. FH treated rats displayed a significant inhibition of lipid peroxidation (LPO) and augmentation of endogenous antioxidants. These results give credence to the notion that treatment with F. hispida leaf extract ameliorates CP induced cardiotoxicity and might serve as a novel combination therapy with CP to combat oxidative stress-mediated myocardial injury.