ABSTRACTAdvancements in immune and targeted therapies have significantly enhanced cancer‐specific outcomes for numerous patients. However, a proportion of these therapies is associated with cardiovascular toxicities, which pose challenges in patient management. Doxorubicin, an antineoplastic agent commonly prescribed for treating malignancies, is particularly notable for its efficacy, however, clinical usage is restricted due to its myocardial toxicity. Bioactive compounds possess immense pharmacological properties and supplementation of bioactive compounds had proven to ameliorate drug‐induced toxicities. In this study, we aimed to evaluate the ameliorative effect of bioactive compound glycitein against DOX‐triggered myocardial toxicity. DOX‐treated Wistar rats were subsequently administered with two different doses of glycitein. The change in body weight and arterial pressure was recorded. After 24 h, the last treatment animals were euthanized, blood and cardiac tissue samples were collected. The levels of C‐RP, uric acid, total protein, lipid peroxidation, and antioxidants were quantified in the experimental animals to assess the impact of glycitein against DOX‐induced oxidative stress. Lipid‐lowering effect and ATPase‐regulating effect of glycitein in DOX‐administered rats were measured. Inflammatory inducers and apoptotic proteins in the DOX‐administered animals were quantified to examine the anti‐inflammatory and antiapoptotic effect of glycitein. Cardiac histopathological examination was performed to ratify the cardioprotective potency of glycitein against DOX. The results of our research prove glycitein treatment scavenged free radicals induced by DOX and rendered lipid‐lowering, anti‐inflammatory, antiapoptotic, and cardioprotective effects in the DOX‐administered rats. Overall, our research concludes that glycitein is a potent bioactive compound which can be supplemented along with doxorubicin in cancer patients to prevent anticancer drug‐induced cardiotoxicity.