Piroxicam is a prominent pain reliever that's accessible in a wide range of dosage forms such as tablets, ointments, and gel. Formerly, multiple approaches for active therapeutic ingredients and tablet dosage forms have been developed. According to the review of the literature, no approaches for piroxicam gel dosage form have been developed. Piroxicam in gel dosage form was estimated using a Reverse phase high-performance liquid chromatography (RP-HPLC) method that is fast, responsive, reliable, and affordable. The analytical method was developed using a Kromacil C18 column (250 X 4.6mm 5 µ with a 25mM KH<inf>2</inf>PO<inf>4</inf> buffer (pH 3.0) and acetonitrile (ACN) during the mobile phase in a (60:40v/v) ratio at 1.0mL/min. The eluent was detected at 325nm using a UV-Visible detection device. Piroxicam elutes after 5.525 minutes. The suggested approach provides linearity of concentration from 4.00 to 12.01 µg/mL, with an r2 value of 0.9998. According to ICH requirements, this method was evaluated for process accuracy, specificity, linearity, dependability, robustness, and ruggedness. © 2025 Elsevier B.V., All rights reserved.