Earthworm powder (EWP), a natural boon for medicine, has showed a wide variety of biological activities, which make it a good candidate for the treatment of many oxidative stress-mediated diseases. The present study is aimed to evaluate its therapeutic potential by estimating the levels of lipid peroxidation and assaying activities for various antioxidants in ISO-induced myocardial infarction bearing rats. Subcutaneous injection of ISO (85mg/kg body weight administered subcutaneously) to Wistar male rats for 2 consecutive days caused myocardial damage in rat heart, which was determined by the increased activity of lipid peroxidation (LPO). The heart tissue antioxidant enzymes, such as glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) and the non-enzymatic antioxidant, like reduced glutathione (GSH), vitamin C and vitamin E levels were altered in MI rats. Further, EWP (200mg/kg body weight suspended in saline) administration attenuated the antioxidant mechanism from lipid peroxidation. Thus, the modulatory effects of EWP on attenuating the lipid peroxidation, upregulation of both enzymic and non-enzymic antioxidants, and DNA fragmentation afford an assurance for the treatment of myocardial infarction in the future.