In this work, advanced method of process control as Extended Prediction Self-Adaptive Control (EPSAC) and Nonlinear Extended Prediction Self-Adaptive Control (NEPSAC) are implemented and compared with the traditional PID controller tuned by a novel KC autotuning method and a classical FRtool method. The controllers are designed based on a linear and non-linear reactor model of the Anaerobic digestion pilot plant located in Peru. The performance evaluation of the controllers is realized through MATLAB environment with model parameters obtained experimentally. Also, a linear model has been developed using a novel estimation method of a Second Order Plus Dead-Time models (SOPDT). The results show that NEPSAC outperforms the other controllers.