Recent surveys show that 18% of adults in the United States use prescription drugs concurrently with herbal or vitamin dietary products. Despite possible dietary supplement-drug interactions through modulation of cytochrome P450s (CYPs), dietary supplements have not been studied at a screening scale to assess their effects on CYPs. In this study, 116 herbal dietary supplements, commercially available for nutrient supply and weight management, were administered to rats to test whether they modulate the expressions of CYP1A2, 2C11, 2D1, 2E1 and 3A1 proteins. Seventy-five percent of the 116 dietary supplements modulated at least one CYP, while 25% had no effect. CYP2C11 protein expression was the most inhibited by supplements (51%), whereas CYP1A2, 2D1, 2E1 and 3A1 were the least inhibited (12-18%). CYP1A2 was the most induced, modulated by 21% supplements, while CYP2E1 and 3A1 were moderately induced (7-8%). CYP2C11 and 2D1 were not induced by any supplement tested in this study. Thus, this study suggests that dietary supplement-drug interactions may occur through modulation of CYPs in humans when they are taken simultaneously.