A novel, sensitive, and green micellar UPLC method was proposed and validated for the simultaneous determination of four hypoglycemic agents used in type II diabetes mellitus treatment namely, pioglitazone, alogliptin, glimepiride, and vildagliptin. The developed UPLC method was successfully applied for quantitative analysis of these drugs in bulk, in pharmaceutical formulations, and in spiked human plasma. Chromatographic separation was carried out on a Kinetex® 1.7 μm XB-C18 100 Å (50 × 2.1 mm) column, using a degassed and filtered mixture of (0.1 M SDS- 0.3% triethyl amine- 0.1% phosphoric acid (pH 6)) and n-propanol (85:15 v/v), at a flow rate of 0.2 mL/min. The experimental conditions of the suggested method were well investigated and optimized. The newly developed micellar UPLC method is capable of determining different dosage forms at the same time with the same solvents, saving time and effort. The method was found to be efficiently applicable in spiked human plasma and could be extended to study the pharmacokinetics of the cited drugs in real human plasma samples. The greenness of the developed method was evaluated by applying the Eco-scale scoring tool, which verified the excellent greenness of the analytical method.