Abstract: Beta-hydroxy-beta-methylglutaryl coenzyme a reductase (HMG CoA reductase) is the key enzyme in cholesterol biosynthesis. Inhibition of this enzyme reduces the synthesis of cholesterol and could be used in the management of coronary artery disease. Drugs used for the management of cholesterol biosynthesis have showed some side effects that are cause of new trends in the nature. This study was designed to find new HMG CoA reductase inhibitors from natural resources. One hundred plants were botanically identified and their methanol extracts were prepared. Anti HMG-CoA reductase activity of the extracts were determined spectrophotometrically by NADPH oxidation, using HMG-CoA as the substrate. Quercus infectoria, Rosa damascena and Myrtus communis extracts showed more than 50% inhibitory effect on the enzyme activity and 21 extracts showed an inhibitory effect between 30-50 percent on activity of HMG-CoA reductase. Kinetic study of the enzyme was performed in the presence of two concentrations of the effective extracts (0.05 and 0.15 mg mL-1). These active extracts showed non-competitive inhibition by Lineweaver-Burk plot analysis. Under the standard condition, Km value for enzyme was 0.6 mM and Vmax value was 0.011 mM min-1. When 0.15 mg mL-1 of extracts of Quercus infectoria, Rosa damascena and Myrtus communis were used the Vmax values of 0.0041, 0.0031 and 0.0028 mM min-1 were obtained, respectively. Therefore, purification and characterization of their active constituents and in vivo examination of these active extracts, is necessary in order to be used as safer therapeutic agents in the future.