A rapid, simple, selective, and specific reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for estimation of Naproxen and Sumatriptan from tablet using spiked human plasma. The chromatographic separation was performed on Phenomenex Luna C18 column (5μm, 25cmx4.6mm id)  with a mobile phase comprised of Acetonitrile: Methanol: phosphate buffer pH 6 (50:10:40 v/v), at a flow rate of 1.0ml/min. The calibration curve was linear in the range of 1-3 µg/ml. The developed method was found to accurate and sensitive. Results of recovery studies prove the extraction efficiency. Stability data indicated that Sumatriptan and Naproxen was stable in plasma after three freeze thaw cycles and upon storage at −20°C for 30 days.