Phloretin is a well-known apple polyphenol possessing a wide variety of biological effects and has been widely used in many fields. However, it's unclear whether phloretin has an effect on the activity of human UGT enzymes. Our study indicated that phloretin inhibited human UGTs on a broad spectrum. Further kinetic analysis revealed that phloretin inhibited UGT1A1, 1A6, 1A9, 2B7, and 2B15 in a noncompetitive manner, with calculated Ki of 8.34 μM, 16.69 μM, 10.58 μM, 17.74 μM and 2.46μΜ, respectively, whereas phloretin inhibited UGT1A7 in an un-competitive manner, with calculated Ki of 5.70 μM. According to the quantitative risk prediction, co-administration of phloretin with drugs primarily metabolized by UGT1A7 and/or UGT2B15 may result in potential food-drug interactions. To sum up, when phloretin or phloretin-rich food is administered with medications metabolized by UGT1A7 and/or UGT2B15, concern should be exercised.