This work describes the application of Fenton’s like system (H2O2/Cu2+) assisted by microwaves to the removal of phenolic compounds from olive mill wastewater (OMWs). The effect of various operating conditions, namely copper ion concentrations (X1), hydrogen peroxide (X2), time of irradiation (X3) and microwave power (X4) were evaluated by factorial design of experiments. Results showed that X1, X2, X3 and X4 had significant effects on the response followed by the interactions X1X2, X1X3, X2X4 and X1X2X3.The highest degradation of phenolic compounds was found for 500 mg/L copper dose, a power of 340 W, 12 M H2O2 and 8 min irradiation time. FTIR analysis confirmed that microwave degradation of polyphenols by means of the Fenton-like system Cu(II)/H2O2 could be an efficient solution for the treatment of olive mill wastewater.