Due to the exhaustion of fossil fuels and environmental degradation, biodiesel has attracted much attention as a new energy source. Currently, microwave reactors are used extensively for producing biodiesel. However, nonuniform heating of producing biodiesel in microwave reactors is a major problem. In order to solve the problem, a microwave reactor with an interlayer which can obviously improve the uniformity of microwave heating was designed. In this work, the heating efficiency and heating uniformity of the reactor were discussed from two aspects of waveguide position and interlayer thickness by means of multi-physical coupling calculation. According to the calculation results, the optimization model of a microwave reactor with an interlayer was obtained. Then, based on the above optimization model of a microwave reactor with an interlayer, a stirrer that can improve the heat transfer of the fluid material was introduced. The Maxwell equation, heat transfer equation, and flow equation were coupled by the multi-physical field simulation method to explore the influence of different factors of the stirrer on power consumption and heating uniformity. Through response surface analysis, it was found that the primary and secondary order of stirring factors affecting microwave heating uniformity was stirring speed > impeller diameter > bottom clearance, and there was an interaction between different factors. From the two aspects of stirring power consumption and heating uniformity, the best stirring effect was obtained.