The present manuscript describes simple, sensitive, rapid, accurate, precise and economical derivative spectroscopic method for the simultaneous determination of Pantoprazole and Levosulpiride in pharmaceutical dosage form. In this study a first-derivative spectroscopic method was used for simultaneous determination of pantoprazole and levosulpiride using the zero-crossing technique. The measurements were carried out at wavelengths of 269 and 249 nm for Pantoprazole and Levosulpiride respectively. The method was found to be linear (r2>0.9929) in the range of 10-50 μg/ml for Pantoprazole at 269 (ZCP of Levosulpiride) nm. The linear correlation was obtained (r2>0.9948) in the range of 10-50 μg/ml for Levosulpiride at 249 (ZCP of Pantoprazole) nm. The limit of determination was 0.69 and 0.58 μg/ml for pantoprazole and levosulpiride respectively. The limit of quantification was 2.06 and 1.69 μg/ml. The method was successfully applied for simultaneous determination of Pantoprazole and Levosulpiride in pharmaceutical dosage form.