This paper focuses on the design method of the optimal multiple inputs and multiple outputs (MIMO) proportional integral derivative (PID) controllers for the MIMO processes via using Lyapunov theorems. A hybrid augmented integral squared error (HAISE) is applied to design the optimal multiloop PID controller for the MIMO plants. The optimal multiloop PID control problem is transformed into a nonlinear constraint optimization (NLCO) problem. The optimal PID controller parameters are obtained from solving the NLCO problem. The design method is applied to devise the multiloop optimal PID controller for different types of MIMO plants and the optimal PID controller under different control weight is shown in this paper. The performances of different PID tuning methods are studied too. The computer simulation results are presented to demonstrate the effectiveness of the design method and good performance and robustness of the optimal multi-loop PID controllers.