Doxorubicin is Anrthacycline derivative and most active cytotoxic agent in current use. It is been using to treat various malignancies but the clinical usefulness has been limited due to its specific cardiac toxicity. The main objective is to study the preventive role of ethanolic extract of whole plant of Boerhaavia diffusa (EEBD) against doxorubicin (Dox) induced myocardial toxicity in rats. Cumulative administration of Dox (2.5 mg/kg for two weeks) was injected to produce cardio toxicity. EEBD (100 and 200 mg/kg, po) was administered as pretreatment for two weeks followed by Dox on alternative days for two weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), Creatine kinase (CK-MB) and cardiac troponin-I (cTnI), biochemical parameters such as aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP), antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) catalase (CAT) and lipid peroxidation were monitored after three weeks of last dose of Dox. Histopathalogic studies of heart were also carried out to evaluate myocardial toxicity. In results the repeated administration of Dox produces cardiomyopathy, which was characterized by increased level of cardiac biomarkers and deficit antioxidant enzymes. Pretreatment with the EEBD (200mg/kg) significantly protected myocardium from the toxic effects of Dox by reducing the elevated level of biomarker enzymes like LDH, CK-MB and absence of cTnI and biochemical parameters such as AST, ALT and ALP reduced to normal. EEBD increased the reduced level of GSH, SOD and CAT while decreased the elevated level of malondialdehyde (MDA) in cardiac tissue. In conclusion the biochemical and histopathological data evidently substantiate the cardio protective effect of EEBD, which could be attributed to its antioxidant property.