This book presents the graduated research in UTM Malaysian, that included the non-linear mathematical model multi-input, multi-output MIMO and simulation of the waste water treatment plane (WWTP) with closed loop PID controller, And is aimed to investigate a new multi-variable control methodology using a self-tuning PID control algorithm to control the concentration of dissolved oxygen and nitrate of a waste water treatment plane. The traditional PID tuning technique is proposed as a point of comparison. Relative Gain Array (RGA) is applied which yields identity matrix for both reduced model. Integral Time Square Error (ITSE) has been chosen as the objective function. Two of intelligent optimization techniques: GSA is proposed in this research, and PSO is from previous research to tune the PID controller parameters.