In this study, inhibition potentials of harmal seed alkaloids and olive leaf polyphenols were investigated on COMT catalyzed methylation reaction. Inhibition performances of natural alkaloids and polyphenolics whose purities were attempted to be increased by extraction and fractionation were compared with standards of these compounds and the best known COMT inhibitor, 3,5-dinitrocatechol. COMT enzyme inhibition experiments were performed with sentitive fluorometric method. In this method, Km values for SAM and aesculetin substrates were found as 3.5 + 0.3 uM and 6.4 + 0.4 uM, respectively. As a result of the inhibition study, the highest inhibitory effect is observed for harmine and harmaline rich fractions among harmal seed alkaloids. Inhibition constants indicating degree of competitiveness and noncompetitiveness (Ki and aKi) of the harmine fraction which has the highest inhibition performance were calculated as 0.15±0.07 ug/ml and 1.28±0.06 ug/ml, respectively.In the studies performed with standards of olive leaf polyphenols, while it was observed that rutin has inhibitory effect, oleuropein was found less effective. However, oleuropein rich fraction of olive leaf extract showed higher inhibitory effect than crude extract and rutin. It was also observed that polyphenolic extracts obtained from vitex, terebinth and mastic leaves showed high inhibition capacities, it was thought that fractionation should be performed for these plants. As a more general conclusion, it was revealed that harmal seed alkaloids and olive leaf fractions with high purity are promising natural COMT inhibitors. By performing this study, the kinetic inhibition constants of extracts, their fractions and standards could be determined and they could be reported into literature.