A simple, rapid, accurate, precise, and economical RP-HPLC method was developed and validated for the estimation of Dexlansoprazole (DXL) and Domperidone (DOM) in pharmaceutical dosage forms. Chromatographic separation was achieved using a Shim-pack C8 column with HPLC grade Acetonitrile: Water (pH adjusted to 3.0, 1% Ortho Phosphoric acid) (40:60 % v/v) as the mobile phase at a flow rate of 1.0 mL/min with UV detection at 210 nm. The method showed linearity over the concentration 20–100 µg/mL for Dexlansoprazole and 10-50 µg/mL for Domperidone with R²value of 0.9983 and 0.9932. Accuracy was confirmed by recovery studies, with recoveries of 98.53–101.25% for DXL and 99.85–101.76% for DOM. Precision showed %RSD below 2%. The method was also validated for LOD, and LOQ according to ICH guidelines and was suitable for routine analysis.