In this research, the optimization of the electrochemical advanced oxidation treatment for the degradation of Clopidogrel was investigated. This study examined the influence of various experimental parameters including applied current, initial Clopidogrel concentration, and ferrous ion concentration by the use of the Doehlert design within a response surface methodology framework. The improved grey wolf optimizer was applied in order to define the optimum operating conditions. The monitoring of clopidogrel concentration during treatment revealed that complete disappearance of clopidogrel was achieved under an initial clopidogrel concentration of 0.02 mM, current intensity of 0.55 A, Fe2+concentration of 0.7 mM, and a reaction time of 20 min in a solution containing 50 mM Na2SO4 at pH 3. A quadratic polynomial model was developed, and its statistical significance was confirmed through the analysis of variance, demonstrating a high level of confidence in the model (R2 = 0.98 and p-value < 0.05). Furthermore, following electrolysis treatment for 480 min, the synthetic clopidogrel solutions underwent mineralization, achieving a 70.4% removal rate of total organic carbon. Subsequently, the applicability of the optimized process was tested on real pharmaceutical wastewater, and mineralization was investigated under the identified optimal conditions, resulting in a total organic carbon removal rate of 87% after 480 min of electrolysis time. The energy consumption for this system was calculated to be 1.4 kWh·kg−1 of the total organic carbon removed. These findings underscore the effectiveness and potential applicability of the electrochemical advanced oxidation for industrial wastewater treatment.