A new simple, accurate, rapid and precise isocratic Reverse Phase High performance liquid chromatographic (HPLC) method was developed and validated for the determination of Esomeprazole (ESO), and Levosulpiride (LEVO) in capsule formulation. The Method employs Shimadzu HPLC system on Hypercil BDS C18 (25 cm × 4.6 mm i.e., 5 µm) and flow rate of 1 ml/min with a load of 20µl. Acetonitrile and Phosphate buffer was used as mobile phase in the composition of 50:50 at 3.5 PH. The Detection was carried out at 240 nm. Linearity ranges for Esomeprazole and Levosulpiride were 20-60 µg/ml, 37.5-225 µg/ml respectively. Retention Time of Levosulpiride and Esomeprazole were found to be 3.367 min, 4.320 min respectively. Percent Recovery study values of Esomeprazole and Levosulpiride were found to be within 98-102%. This newly developed method was successfully utilized for the Quantitative estimation of Esomeprazole and Levosulpiride in pharmaceutical dosage forms. This method was validated for accuracy, precision, linearity and Robustness as per ICH guidelines.