Objective:A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for rapid determination of empagliflozin, linagliptin, saxagliptin and alogliptin in health foods.Methods:Target compounds in samples were ultrasonically extracted by methanol, separated by reverse liquid chromatography and detected by electrospray ionization (ESI) using multiple reaction monitoring (MRM) mode. The quantitation was carried out by external standard method of matrix calibration curve.Results:Good linear relationship displayed in the concentration range of 2~100 μg/L for saxagliptin and alogliptin, with the limits of quantitation (LOQs) of saxagliptin and alogliptin of 0.10 mg/kg. At three spiked concentration levels of 0.1, 0.2 and 1.0 mg/kg, the recoveries were 79.2%~113.0%, with relative standard deviations (RSDs) of 0.9%~8.4%. The linear ranges of empagliflozin and linagliptin were 20~500 μg/L with LOQs of empagliflozin and linagliptin were 1.00 mg/kg. The recoveries were 77.5%~111.1% with relative standard deviations(RSDs) of 2.5%~9.4% at three spiked concentration levels of 1.0, 2.0 and 10.0 mg/kg.Conclusion:The method is simple, rapid, accurate and suitable for identification and determination of 4 anti-diabetic medicines in health foods.