Tolmetin sodium (TOL) is a non-steroidal anti-inflammatory drug used to treat arthritis. Potentiometric ion selective electrodes (ISEs) bypass sample pre-treatment, high-tech apparatus, and toxic chemicals. The current study aimed to develop and validate a potentiometric analyser for the direct assay of TOL in pharmaceutical dosage form and human plasma. We designed an experimental approach to determine the factors that affect the performance of the developed sensor. A solid contact glassy carbon electrode was utilized as a support for the developed sensor. The interaction of TOL with several ionophore was studied using molecular docking. The optimized sensor was fabricated using dioctyl phthalate as plasticizer, tetra dodecyl ammonium bromide as anion exchanger, and β cyclodextrin as ionophore. The sensor achieved -58.78 Nernstian response within 1.00×10-2 to 2.00×10-6 mol/L linear range,1.56 ×10-6 mol/L LOD, and fast response within 7 s. The greenness of the proposed method was assessed using the Analytical Eco-scale and the "Green Analytical Procedure Index" metric tools and compared with the reported methods and gained high scores. The proposed method has several advantages in encouraging quality control and clinical labs to routinely use the developed sensor in the assay of TOL in pharmaceutical dosage forms and human plasma.