Olive oil mill wastewater (OMW) is environmentally hazardous not only because it contains high recalcitrant and toxic compounds, but also due to its high organic load and turbidity. In this study, oxidation of OMW by microwave (MW)-activated persulfate is investigated. Box-Behnken design is applied to investigate the effects of operating conditions on operating cost, organic matter, and color removal. Multi response optimization is performed according to minimum operating cost, maximum organic matter and color removal efficiencies. At optimum conditions (persulfate anion dose of 266 g L-1, oxidation duration of 23.58 min, MW power of 567 W, and initial pH 2), chemical oxygen demand (COD) removal of 63.38%, color removal of 94.85%, and operating cost of 0.0633 Euro/g total organic carbon (TOC) removal are found. The biochemical oxygen demand (BOD5)/COD ratio is increased from 0.144 to 0.285. Results of Pareto analysis show individual effect of MW power is 92.81% for TOC removal, 15.52% for color removal, 68.99% for operating cost, respectively. According to the results, it is not recommended to use this process as an ultimate treatment unit due to the high amount of oxidizing agent consumed. Instead, it is recommended to be used as a pre- or post-treatment step.