Single degree-of-freedom (DOF) mechanisms have been widely used for their simple structure and easy to control, but it can only lead through one specific motion trajectory. This article proposes an approach to design multi-mode single-DOF (MMSD) four-bar mechanisms, which could realize multiple motion trajectories using only one driving motor via an optimized structure with a selected adjustable parameter, which is applied in the design of upper limb rehabilitation mechanism. Firstly, three target trajectories are established for the upper limb rehab of three different groups of population. Then a source mechanism for multi-mode four bar linkage with five candidate adjustable parameters is designed, which can fit multiple different motion trajectories by selecting one specific parameter to be adjustable. Next, multi-objective optimization algorithm MSOPS-II is adopted to analyze the Pareto boundary, and HV value is evaluated to determine the optimal adjustable parameter, while the rest fixed parameters are also obtained through optimization. Finally, the multi-trajectory fitting results with the MMSD four-bar mechanism are presented and a comparison of various multi-objective optimization algorithms is con-ducted to assess the fitting errors under three different modes. The prototype of the multi-mode upper limb rehabilitation device is also designed.