A rapid, simple, sensitive, precise and specific square wave voltammetric method was developed for the simultaneous determination of Thiocolchicoside (TC) and Diclofenac diethyl ammonium (DDA) in topical gel formulation. The combination of TC and DDA have synergetic action on the treatment of rheumatoid arthritis and other related conditions. The optimum conditions were obtained in Britton–Robinson buffer pH 3.00 for electroreduction at hanging mercury drop electrode. Well-defined peaks were observed for TC at –0.85 V, and for DDA at –1.18 V vs. Ag/AgCl/4.6 M KCl. Under optimum conditions, the linear response ranges for determination of TC and DDA were 1.07–24.2 µM and 5.64–45.8 µM, with detection limits of 0.54 and 3.25 µM, respectively. The electrochemical behaviors of the substances such as current type and reversibility of the electrode reactions were investigated by using cyclic voltammetry. The reduction mechanisms were also proposed. The method was validated with respect to accuracy, precision, sensitivity and specificity according to the International Conference on Harmonization guidelines. The developed method was applied for the simultaneous determination of TC and DDA in topical gel formulation including binary mixtures. The excipients present in the formulation did not interfere with the assay. The method is suitable for application in quality-control laboratories, because it is simple and rapid with high accuracy and precision.