The production of biodiesel through a transesterification method produces a large amount of wastewater that contains high levels of chemical oxygen demand (COD) and oil and grease (O&G). Currently, flotation is the conventional primary treatment for O&G removal prior to biological treatments. In this study, electrocoagulation (EC) was adopted to treat the biodiesel wastewater. The effects of initial pH, applied voltage, and reaction time on the EC process for the removal of COD, O&G, and suspended solids (SS) were investigated using one factor at a time experiment. Furthermore, the Box-Behnken design, an experimental design for response surface methodology (RSM), was used to create a set of 15 experimental runs needed for optimizing of the operating conditions. Quadratic regression models with estimated coefficients were developed to describe the pollutant removals. The experimental results show that EC could effectively reduce COD, O&G, and SS by 55.43%, 98.42%, and 96.59%, respectively, at the optimum conditions of pH 6.06, applied voltage 18.2 V, and reaction time 23.5 min. The experimental observations were in reasonable agreement with the modeled values.