This paper focuses on the design method of optimal multi-loop proportional integral (PI) controllers for the multiple inputs and multiple outputs (MIMO) systems via using Lyapunov theorems. The design problem of optimal multi-loop PI controller is transformed into a nonlinear constraint optimization (NLCO) problem. The optimal multi-loop PI controller parameters are obtained from solving the NLCO problem. The design method is used to devise the multi-loop optimal PI controller for different types of MIMO plants, and the optimal multi-loop PI controller under different control weight is also given too. The performances and robustness of different multi-loop PI controller's tuning methods are studied. The computer simulation results are presented to demonstrate the design method's effectiveness and optimal MIMO PI controller's better performance and robustness.