An altered lipid profile may lead to the development of CVD. We evaluated the protective role of baicalein (BAC) against lipidemic and oxidative stress in hyperlipidemic challenged Wistar rats. Male Wistar rats were given a high-fat diet (HFD) (suspension (w/v) of 0.5% cholesterol, 3% coconut oil and 0.25% cholic acid for 30 days) to create a hyperlipidemic model. BAC was supplemented to experimental rats (80 mg/kg body weight). Biomarkers of oxidative stress including ROS, FRAP, GSH, PMRS, AGE, MDA, PCO, AOPP, and other parameters (Paraoxonase-1, SGOT, SGPT) including TNF-α and IL-6, were estimated in blood. Oxidative stress and inflammatory markers were significantly increased in the HFD treated group. BAC treatment protected rats from HFD mediated alterations. Our results indicate that baicalein provides protection against hyperlipidemic stress and redox imbalance induced by HFD in rats.