The purpose of this research was to develop a robust, rapid, and novel high-performance thin layer chromatographic (HPTLC) method for quantitation and separation of Lisinopril and Amlodipine in combine tablet dosage form using a quality by design approach. A central composite experimental design with response surface methodology was utilized to study the effects of chromatographic chamber saturation time, band length on Rf value. The Rf value was predicted for Lisinopril and Amlodipine between 0.25 and 0.85 to optimize the chromatographic conditions based on the preliminary trials. The optimized chromatographic conditions were 15 Minute saturation time, 6 mm band length and Methanol: Toluene: Formic acid (8:2:0.2 v/v/v) as a mobile phase. The optimized HPTLC method was validated according to ICH Q2 (R1) guideline. The result of this research clearly shows that QbD approach is successfully applied to optimize HPTLC method through minimum number of experimental runs.