A simple, precise, rapid, and reproducible reversed-phase high-performance liquid chromatography method is developed for the simultaneous estimation of metformin hydrochloride (MET), pioglitazone hydrochloride (PIO), and glimepiride (GLP) present in multicomponent dosage forms. Chromatography is carried out isocratically at 25 degrees C 0.5 degrees C on an Inertsil-ODS-3 (C-18) Column (250 x 4.60 mm, 5 microm) with a mobile phase composed of methanol-phosphate buffer (pH 4.3) in the ratio of 75:25 v/v at a flow rate of 1 mL/min. Detection is carried out using a UV-PDA detector at 258 nm. Parameters such as linearity, precision, accuracy, recovery, specificity, and ruggedness are studied as reported in the International Conference on Harmonization guidelines. The retention times for MET, PIO, and GLP are 2.66 + 0.5 min, 7.12 + 0.5 min, and 10.17 + 0.5 min, respectively. The linearity range and percentage recoveries for MET, PIO, and GLP are 10-5000, 10-150, and 1-10 microg/mL and 100.4%, 100.06%, and 100.2%, respectively. The correlation coefficients for all components are close to 1.