The present study was aimed at evaluating protective role of Eugenia jambolana seed extract (EJSE) on high cholesterol diet (HCD) induced hyperlipidemia/hypercholesterolemia amounting to cardiac and hepatic oxidative stress. Serum markers of cardiac and hepatic damage, total lipid profile (serum, tissue and feces), lipid peroxidation, antioxidant status and histopathological changes in cardiac and hepatic tissue have been assessed in control, HCD fed and HCD+EJSE treated (100 mg/kg BW, p.o.) rats. It was observed that co-supplementation of EJSE to HCD fed rats significantly (p < 0.05) minimized elevation in the serum, and tissue lipid profiles, decrement in the HDL level and resulted in higher elimination of lipids through feces. Also, EJSE successfully ameliorated HCD induced cardiac and hepatic oxidative stress (p < 0.05) and histopathological damage. It can be concluded that, EJSE has the potential of preventing HCD induced experimental hypercholesterolemia and, related cardiac and hepatic oxidative stress. Its therapeutic potential against HCD induced hypercholesterolemia and subsequent oxidative stress mediated cardiac and hepatic damage is indicated.