A method for determining the active pharmaceutical ingredient and combination dosage form of pioglitazone hydrochloride (PIO) and vildagliptin (VILDA) was developed and validated using a stability-indicating high-performance thin-layer chromatography (HPTLC) method. From the literature review, it was found that there is no reported HPTLC method for the simultaneous determination of PIO and VILDA. Hence, this method was developed. The silica gel 60 F254 HPTLC plates were used as the stationary phase. The mobile phase used in this research work contains methanol‒toluene‒ethyl acetate‒triethylamine (2:6:2:0.1, V/V). The International Council for Harmonisation (ICH) requirements were followed in the validation of the developed method. Correlation coefficients (r2) for PIO and VILDA at concentration ranges of 1.5‒9 and 5‒30 µg/band were 0.9901 and 0.9922, respectively. The percentage recoveries for PIO and VILDA were found to be 98.99‒101.84 and 98.18‒101.78. For interday precision, the percentage relative standard deviation (%RSD) values for PIO and VILDA were found to be 0.05‒0.10 and 0.15‒0.56. For intraday precision, the %RSD values for PIO and VILDA were found to be 0.49‒1.14 and 1.66‒1.76. The limit of detection (LOD) values for PIO and VILDA were found to be 0.15 and 0.48 µg/band, respectively. The limit of quantification (LOQ) values for PIO and VILDA were found to be 0.44 and 1.47 µg/band, respectively. The robustness study was performed by implementing deliberate changes in the mobile phase composition and saturation time, the %RSD values for PIO and VILDA were within the acceptable limits. The forced degradation study was performed in acidic, basic, oxidative, and hydrolytic conditions. PIO was found to be stable in oxidative condition, while VILDA was found to be stable in basic and neutral conditions. The developed method passes all the ICH criteria; hence, the developed method is accurate, easy, suitable, and stable for the analysis of PIO and VILDA in combined dosage form.