Currently, rehabilitation systems with closed kinematic chain mechanisms are low-cost alternatives for treatment and health care. In designing these systems, the dimensional synthesis is commonly stated as a constrained optimization problem to achieve repetitive rehabilitation movements, and metaheuristic algorithms for constrained problems are promising methods for searching solutions in the complex search space. The Constraint Handling Techniques (CHTs) in metaheuristic algorithms have different capacities to explore and exploit the search space. However, the study of the relationship in the CHT performance of the mechanism dimensional synthesis for rehabilitation systems has not been addressed, resulting in an important gap in the literature of such problems. In this paper, we present a comparative empirical study to investigate the influence of four CHTs (penalty function, feasibility rules, stochastic-ranking, and ϵ-constraint) on the performance of ten representative algorithms that have been reported in the literature for solving mechanism synthesis for rehabilitation (four-bar linkage, eight-bar linkage, and cam-linkage mechanisms). The study involves analysis of the overall performance, six performance metrics, and evaluation of the obtained mechanism. This identified that feasibility rules usually led to efficient optimization for most analyzed algorithms and presented more consistency of the obtained results in these kinds of problems.