This research was designed to determine about the possible potency of medicinal plants Viscum album L. and its major polyphenolic ingredient, o-coumaric acid on rat liver cholesterol and bile acid metabolizing enzymes. Bioactive compounds of V. album extracts were identified using LC-MS technique. The water extracts of V. album (10 mg/kg) and o-coumaric acid (30 mg/kg) were injected intraperitoneally for 9 days. Then, in vivo effects of this plant and its major phenolic ingredient (o-coumaric acid) on rat liver cholesterol and bile acid metabolizing cytochromes P450s were analyzed by determining protein and mRNA expression levels using western blotting and qRT-PCR techniques, respectively. The results showed that V. album caused a 0.9 fold decrease in protein expression of CYP7A1 and CYP7B1, but 1.4 and 1.3 fold increases in protein expression of CYP27A1 and CYP8B I, respectively. V. album caused 9, 1.3 and 2.4 fold decrease in mRNA expression of CYP7A1, CYP27A1, CYP7B1, respectively, however, 4.2 fold increase in mRNA expression of CYP8B1. Injection of o-coumaric acid to rats resulted 0.8 fold decrease in protein expression of CYP7A1, CYP27A1, CYP8B1 and CYP7B1. However, o-coumaric acid caused 1.8, 1.3, 2.3 and 2.3 fold increase in mRNA expression of CYP7A1, CYP27A1, CYP8B 1 and CYP7B1, respectively. According to results, even though V. album and o-coumaric acid caused fold change in protein and mRNA expressions of bile acid metabolizing CYPs, serum cholesterol levels remained unchanged. Thus, the idea can be taken about the role of this plant and its major polyphenolic ingredient in drug discovery and development.