This paper describes a simulation-based study in MATLAB/Simulink to select an appropriate controller for the 3-PRRR (P – Prismatic, R – Revolute) Cartesian Parallel Manipulator (CPM) suitable for lower limb rehabilitation therapies. The dynamic performance of the CPM is incorporated into the simulation model through the derived inverse kinematic equations and assigning the dynamic parameters of the CPM through SimMechanics in MATLAB. This study compares the performance accuracy of the Proportional Integral Derivative (PID) controller, Sliding Mode Control (SMC), and Model Predictive Controller (MPC) to enable real-time tracking of the end effector. It is intended to implement the controller with the least error to the 3-PRRR hardware for superior tracking efficiency of the desired trajectory. Finally, the effectiveness of the 3-PRRR CPM for lower limb rehabilitation with the proposed motion controller is simulated and analyzed in Simulink. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.