Statistical analysis was applied to optimize the electrochemical mineralization of ibuprofen with two boron-doped diamond (BDD) electrodes in a continuous electrochemical flow reactor under recirculation batch mode. A central composite rotatable (CCR) experimental design was used to analyze the effect of initial pH (2.95−13.04), current intensity (2.66−4.34 A), and volumetric flow rate (0.16−1.84 L/min) and further optimized by response surface methodology (RSM) to obtain the maximum mineralization efficiency and the minimum specific energy consumption. A 91.6% mineralization efficiency (EM) of ibuprofen with a specific energy consumption (EC) of 4.36 KW h/g TOC within 7 h of treatment was achieved using the optimized operating parameters (pH0 = 12.29, I = 3.26 A, and Q of 1 L/min). Experimental results of RSM were fitted via a third-degree polynomial regression equation having the performance index determination coefficients (R2) of 0.8658 and 0.8468 for the EM and EC, respectively. The reduced root-mean-square error (RMSE) was 0.1038 and 0.1918 for EM and EC, respectively. This indicates an efficient predictive performance to optimize the operating parameters of the electrochemical flow reactor with desirability of 0.9999993. Besides, it was concluded that the optimized conditions allow to achieve a high percentage of ibuprofen mineralization (91.6%) and a cost of 0.002 USD $/L. Therefore, the assessed process is efficient for wastewater remediation.”