Objective: Dietary changes playmajor risk roles in oxidative stress andcardiovascular disease and modulate normal metabolic function. The present study was designed to investigate the ameliorative potential of different extracts of Hemidesmus indicus to experimental high-fat diet in wistar rats, and their possible mechanism of action.  Materials and Methods: Male wistar rats were divided into 6 groups (n=6/group) andfed with a standard diet (control), high-fat diet (HFD), high-fat diet supplemented with different extracts and positive control for 9 weeks. High-fat diet induced changes in average body weight andoxidative stress and elevated levels of plasma lipid profilein rats. Results: Oral administration of methanolic extract of H. indicus(200 mg/kg) offered a significant dose-dependent protection against HFD-induced oxidative stress, as reflected in the levels of catalase (pConclusion: The present study revealed that the methanolic extract of H.indicus protects against oxidative stress, hyperlipidemia and liver damage.