Wastewater reuse is one of the most important successful methods to overcome the problem of water shortage. But one of the major barriers to wastewater reuse is concerned about the health risk of exposing public to treated wastewater and associated chemical and microbial contaminants. For this reason, treated wastewater disinfection is necessary to avoid sanitary risks. The conventional methods of wastewater disinfection are chemical process, chlorination, ozonation, UV radiation and etc. However, these technologies have some disadvantages and drawbacks. In recent years, there has been growing an interest in Advanced Oxidation Processes (AOPs) for their application in the field of water and wastewater treatment. Among AOPs, the Electro-Fenton process (EFP), has been applied to degrade organic compounds that present in polluted wastewater by using the coupling of electrochemical and Fenton’s reaction. The aim of this study was to evaluation the efficiency of Electro-Fenton method to reduce coliform and organic loads of treated municipal wastewater. Tests were performed on secondary effluent of the Isfahan south municipal wastewater treatment plant. Wastewater treated by using an electrolytic cell that consists of two iron and graphite electrodes as anode and cathode, and an electrical supply direct current. In this study, the effective parameters on efficiency of the process including time, concentration of hydrogen peroxide ( ), distance between the anode and cathode, anode surface area and pH were studied in three levels. Total coliform (TC) and fecal coliform (FC) were analyzed as microbiological parameters and COD, TSS, pH and temperature were tested as physicochemical parameters in all of the effluent samples, before and after the process. In this research, response surface methodology (RSM) and central composite design (CCD) were employed to model, optimize and assess the individual and interactive effects of the five main independent parameters. According to the results of this study, the COD removal efficiency under optimal conditions was obtained 98%. Optimal conditions were obtained when: H is 4.4, the reaction time is 33 minutes, concentration of hydrogen peroxide is 60 mg/L, distance is 4 and surface is 90. The optimal efficiency of log reduction of total coliform was 5.4 and optimal conditions were obtained when: H is 2.55, reaction time is 35 minutes, concentration of hydrogen peroxide is 46 mg/L, distance is 5.5cm and surface is 12 cm 2 . The optimal efficiency for fecal coliform was 6 and optimal conditions were obtained when: H is 2, reaction time is 29 minutes, concentration of hydrogen peroxide is 52 mg/L, distance is 5.6 cm and surface is 10 . Coefficient was obtained 0.91, 0.93 and 0.92 for COD, total coliform and fecal coliform respectively. A high coefficient ensures a satisfactory adjustment of the quadratic model to the experimental data. Due to the reduction in COD and total and fecal coliform bacteria in optimal conditions, it can be concluded that Electro-Fenton is an efficient process in removing high concentrations of pathogenic microorganisms and organic pollution from treated municipal wastewater. The electro-fenton process in optimal conditions, could be met the standards of 1000 TC, and 400FC/100ml for effluent discharge to receive w