Chemometric method – The response surface method was developed for simultaneous spectrophotometric estimation of Esomeprazole and Domperidone in pure form and its pharmaceutical dosage form without any pre-treatment. In the present work, Esomeprazole and Domperidone were dissolved in ethanol and diluted to get a concentration of 10 µg / ml. The solutions were scanned in the UV region in the wavelength range from 200 – 400 nm against ethanol as blank. From the spectrum, it was found that Esomeprazole and Domperidone showed the maximum absorbance at 301nm and 290 nm respectively. Beer’s law was obeyed for the drugs in the concentration range of 4-24 µg/ml for Esomeprazole and 3-18 µg/ml for Domperidone.