Cassia mimosoides Linn has been used from ancient times and used for treating hepatitis for its supposedly medically beneficial properties. In this study, different constituents of the Cassia mimosoides Linn (β-Sitosterol, Oleanolic Acid, Emodin, Carotene, Resorcinol, Luteolin, and α-L-Rhamnose) were evaluated for potential anti-HMG-CoA reductase effect. The inhibitory effects of HMG-CoA reductase of Cassia mimosoides Linn extracts and Pravastatin inhibitor at different concentrations (at doses of 1, 5, 25 or 125 μg/mL, respectively) in reaction system (70 mmol/L phosphate buffer, 200mmol/L NADPH, 5 μg HMG-CoA reductase, 2 mmol/L EDTA, 2 mmol/L cysteamine, 0.06% BSA) into 37°C preheat HMG-CoA for initiating this reaction, and then determined the change of HMG-CoA reductase activity (ΔAΔt) at 340 nm, the inhibition ratio of HMG-CoA reductase activity and its dynamic change of inhibitory effect within 15 min and the descent rate of NADPH. Emodin, Luteolin, β-Sitosterol, Oleanolic Acid, α-L-Rhamnose and Carotene showed good inhibition of HMG-CoA reductase activity. Among them, only the Emodin (1 and 5 μg/mL) groups showed a significant decrease of HMG-CoA reductase activity compared to the Pravastatin (1 and 5 μg/mL) groups respectively. In addition, the HMG-CoA reductase activity in the Emodin and Luteolin (25 and 125 μg/mL) groups was clearly lower than the Pravastatin (25 and 125 μg/mL) groups respectively. And the Emodin and Luteolin (1, 5, 25 or 125 μg/mL) groups exhibited a stable effect on inhibiting the HMG-CoA reductase within 15 min. These findings further support the exploration of Cassia mimosoides Linn as a potential agent for the treatment of hepatitis in future studies.