Abstract: OBJECTIVE To study the effects of magnolol and honokiol on the 7 subtypes of CYP450 enzymes in Magnoliae Officinalis Cortex, and to predict the possible drug-drug interactions. To provide theoretical basis for the clinical application of traditional Chinese medicine. METHODS Used the Cocktail probe method, magnolol, honokiol and CYP450 enzyme specific substrates for 7 subtypes:Tolbutamide (CYP2C), Coumarin (CYP2A6), Dextromethorphan (CYP2D6), Chlorzoxazone (CYP2E1), Testosterone (CYP3A), Phenacetin (CYP1A2), Bupropion (CYP2B6) incubation reaction with rat liver microsomes, combined with UPLC-MS/MS multiple reaction monitoring technology, Determination of the peaks of the corresponding 7 metabolites (4-hydroxytoluidine, 7-hydroxycoumarin, dextrorphan, 6-hydroxy chlorzoxazone, 6-hydroxytestosterone, acetaminophen, and hydroxyacetone) area. By comparing with the control group, the effect of magnolol and honokiol on the activity of the above 7 enzymes was determined, and the corresponding IC₅₀ was calculated to evaluate whether there is an inhibitory effect. RESULTS Magnolol and honokiol had inhibitory effects on the activity of 7 isoforms (CYP2C, CYP2D6, CYP2E1 and CYP2B6) in rat liver microsomes. And that was an increase in mechanical inhibition with increasing compound concentration and pre-incubation time. However the subtypes of enzymes (CYP2A6, CYP3A4 and CYP1A2) did not exhibit this inhibition pattern. CONCLUSION It is likely to inhibit drug metabolism and produce drug-drug interactions, during the combination of magnolia and drugs metabolized by 4 enzymes (CYP2C, CYP2D6, CYP2E1 and CYP2B6). This study also provides very important data support for the clinical application of Chinese herbal medicine Magnoliae Officinalis Cortex and the development of new drugs.