<p>A Design of expert approach was used to develop and validate a high-performance thin layer chromatography method for simultaneously determining Teneligliptin hydrobromide hydrate, Metformin hydrochloride, and Pioglitazone hydrochloride in tablets. The chromatographic conditions for thin layer chromatography were optimized using the Box–Behnken design. The acetone volume, the solvent front, and the saturation time were the three variables used for the chromatographic optimization. The process was confirmed to adhere to ICH guidelines. The linear concentration range for method was 1500–7500 ng/band for Pioglitazone Hydrochloride, 1000–5000 ng/band for Teneligliptin Hydrobromide Hydrate, and 1000–5000 ng/band for Metformin Hydrochloride. All drugs were separated using the optimized mobile phase of toluene: acetone: ammonium acetate (3% w/v): triethylamine (7:1.5:2.5:0.1 v/v/v/v). The R_f values ​​of Teneligliptin Hydrobromide hydrate, Metformin hydrochloride, and Pioglitazone Hydrochloride measured at 245&#xa0;nm were 0.61, 0.18, and 0.68, respectively. The %RSD values for the method validation parameters were all below 2, demonstrating that the method was successfully validated in accordance with regulatory guidelines. The suggested approach is accurate, dependable, specific, and suitable for regular analysis.</p>