<p>A stability-indicating high-performance thin-layer chromatographic (HPTLC) method was developed for the simultaneous determination of sitagliptin phosphate monohydrate and pioglitazone hydrochloride in a combined antidiabetic mixture. Chromatographic optimization was achieved using 10&#xa0;cm × 10&#xa0;cm aluminum-backed silica gel 60 F₂₅₄ plates as the stationary phase and a mobile phase of methanol, toluene, ethyl acetate, and triethylamine (4.0:4.0:2.0:0.5, v/v/v/v). The chamber was saturated for 30&#xa0;min, solvent migration was maintained at 80&#xa0;mm, and densitometric scanning was performed at wavelength 270&#xa0;nm at a controlled temperature of 30&#xa0;°C, yielding sharp, well-resolved bands for both drugs within their respective linear ranges. The method was validated in accordance with ICH Q2(R2) requirements and demonstrated satisfactory levels of precision, accuracy, sensitivity, and robustness. The degradation products were clearly separated from the parent compounds under various forced-degradation conditions (acidic, alkaline, oxidative, thermal, and photolytic stress), thereby confirming the stability-indicating capability of the method. The greenness evaluation was carried out using AGREE, the Eco-Scale assessment, BAGI, and CACI. All four tools indicated favorable environmental performance, characterized by low solvent toxicity, reduced analytical waste, and a balanced integration of analytical efficiency with sustainability principles. Overall, the proposed HPTLC method is reliable, economical, and environmentally benign, making it suitable for routine quality control and stability assessment of sitagliptin phosphate monohydrate and pioglitazone hydrochloride in bulk materials and laboratory-prepared combined formulation.</p>