This work deals with the problem of choosing a controller for the production of biodiesel from the transesterification process through temperature control of the chemical reactor, from the point of view of automatic control, by considering such aspects as the performance metrics based on the error and the energy used by the controller, as well as the evaluation of the control system before disturbances. In addition, an improvement method is proposed via a neuro-fuzzy controller tuned with a metaheuristic algorithm to increase the efficiency of the chemical reaction in the reactor. A clear improvement is shown in the minimization of the integral of time multiplied squared error criterion (ITAE) performance index with respect to the proposed method (8.1657 ×104) in relation to the PID controller (7.8770 ×107). Moreover, the integral of the total control variation (TVU) performance index is also shown to evaluate the power used by the neuro-fuzzy controller (25.7697), while the PID controller obtains an index of (32.0287); this metric is especially relevant because it is related to the functional requirements of the system since it quantifies the variations of the control signal.