Abstract: The uptake of oral administered drugs primarily occurs in the small intestine，which also has the capability to metabolize drugs.Both phase I and phase II metabolic enzymes were expressed in the intestinal mucosa，and cytochromes P450(CYP450s) are the principle enzymes attributed to the biotransformation of drugs.CYP3A and CYP2C are the most abundant subfamilies，accounting for approximately 80% and 16% of total CYP450s in the intestine.Compared to the liver，the expression and activity of CYP450 enzymes in the intestine was susceptible to inducers or inhibitors，leading to drug-drug interaction.This article reviews the expression of CYP enzymes in small intestine and the role of the gut wall in CYP-mediated xenobiotic metabolism.Possible drug-drug interactions due to induction or inhibition of CYP enzymes in the small intestine are also addressed.