Drug counterfeiting is a rising problem due to difficulties with identifying counterfeit drugs and the lack of regulations and legislation in developing countries. This study aims to develop a robust and economic reversed phase high performance liquid chromatography (LC) method for simultaneously determining metformin HCl, vildagliptin, saxagliptin, alogliptin benzoate, sitagliptin phosphate monohydrate, and linagliptin to target counterfeiting. Plackett-Burman (PB) and Box-Behnken (BB) designs were used to screen and optimize the mobile phase composition. Chromatographic separation was carried out on an Inertsil® ODS-3 C18 column with isocratic elution mode and the mobile phase was a mixture of acetonitrile-methanol-ammonium formate buffer, pH 3.5 (25:10:65, v/v/v). This method was applied to analyze synthetic drugs in three traditional Chinese and Indian herbal medicines. To identify the adulterants, thin-layer chromatography (TLC), nuclear magnetic resonance (NMR), and mass spectrometry (MS) were used on counterfeit herbal medicines. The developed method is sensitive, simple, rapid, economical, accurate, and highly robust. Student's t-test and variance ratio (F-test at P < 0.05) were used to compare the results statistically with the reference methods. The study found that the analyzed herbal medicines were adulterated with metformin and the quantification of anti-diabetic counterfeits was therefore applied. This study determined counterfeited anti-diabetic drugs in Indian and Chinese traditional herbal medicines(THMs). Design-of-experiment, PB, and BB designs were used. Method validation was also performed in accordance with the International Conference on Harmonization guidelines.