Abstract: This study investigated the effects of selected Malaysian medicinal plant extracts towards human recombinant cytochrome P450 (CYP450) enzyme activities in vitro. Five Malaysian medicinal plants were tested on the three main CYP450 enzyme activities of CYP2C9, CYP2D6 and CYP3A4. The abilities of these extracts to inhibit human cytochrome P450 enzyme activities were analyzed using a luminescent assay. Orthosiphon stamineus showed the most potent inhibitory activity against CYP2C9 with an apparent IC50 value of 77.5±1.1 μg mL-1, while Andrographis paniculata, Curcuma xanthorrhiza, Eurycoma longifolia and Mitragyna speciosa extracts showed negligible inhibition. On the metabolism mediated by CYP2D6, Mitragyna speciosa showed the most potent inhibitory activities with IC50 values of 3.6±0.1 μg mL-1, followed by Orthosiphon stamineus, Andrographis paniculata and Curcuma xanthorrhiza with IC50 value of 11.7±1.1, 44.2±4.5 and 215.3±71.6 μg mL-1, respectively. Andrographis paniculata ethanolic extract gave the lowest IC50 value towards CYP3A4 with an apparent IC50 value of 27.6±3.7 μg mL-1, followed by Orthosiphon stamineus (78.4±20.3 μg mL-1), Mitragyna speciosa (142.8±13.8 μg mL-1) and Curcuma xanthorrhiza (285.3±61.7 μg mL-1). Sulfaphenazole, quinidine and ketoconazole were used as positive controls for CYP2C9, CYP2D6 and CYP3A4 respectively. The findings suggest that Orthosiphon stamineus, Mitragyna speciosa and Andrographis paniculata may contribute to herb-drug interactions if they are administered concomitantly with drugs metabolized by CYP2C9, CYP2D6 and CYP3A4 respectively.