Adulterating herbal and dietary supplements with synthetic hypoglycemics is widely practiced, especially in developing and undeveloped countries. A simple, precise, and novel method was developed to simultaneously determine synthetic antidiabetics belonging to different classes, namely biguanide, sulfonylurea, and thiazolidinedione, in counterfeit herbal products as adulterants using HPTLC-MS. The method can simultaneously identify and quantify undeclared synthetic drugs metformin, pioglitazone, glipizide, and glimepiride in herbal as well as dietary supplements. The optimized mobile phase for the TLC system consists of cyclohexane:dichloromethane:1-propanol:saturated solution of ammonium acetate in acetic acid in the ratio of (7:5:2:2, v/v/v/v). The method is highly selective and sensitive for detecting chemicals in complex herbal molecules. Identification and quantification of drugs were performed using the densitometric method. The drugs were confirmed using triple quadrupole mass spectrometry through the MS interface. The screening of market preparations revealed the presence of metformin in two of eight products. This study shows that the method for simultaneous determination of these four drugs can be applied successfully to screen synthetic antidiabetics in the herbal complex matrix as adulterants. [ABSTRACT FROM AUTHOR]