Piano-based occupational therapy has emerged as an engaging and effective rehabilitation strategy for improving upper limb motor functions. However, a lack of comprehensive biomechanical modeling, objective rehabilitation assessment, and real-time fatigue monitoring has limited its clinical optimization. This study developed a comprehensive “key–finger–exoskeleton” biomechanical model based on Hill-type muscle dynamics and rigid-body kinematics. A three-dimensional muscle synergy analysis method using non-negative tensor factorization (NTF) was proposed to quantitatively assess rehabilitation effectiveness. Furthermore, a real-time Comprehensive Muscle Fatigue Index (CMFI) based on multi-muscle coordination was designed for fatigue monitoring during therapy. Experimental validations demonstrated that the biomechanical model accurately predicted interaction forces during piano-playing tasks. After three weeks of therapy, patients exhibited increased synergy modes and significantly improved similarities with healthy subjects across spatial, temporal, and frequency domains, particularly in the temporal domain. The CMFI showed strong correlation (r > 0.83, p < 0.001) with subjective fatigue ratings, confirming its effectiveness in real-time fatigue assessment and training adjustment. The integration of biomechanical modeling, synergy-based rehabilitation evaluation, and real-time fatigue monitoring offers an objective, quantitative framework for optimizing piano-based rehabilitation. These findings provide important foundations for developing intelligent, adaptive rehabilitation systems.

This study developed and evaluated a novel upper-limb rehabilitation device that integrates piano playing into task-oriented occupational therapy, addressing the limitations of traditional continuous passive motion (CPM) training in patient engagement and functional recovery. The system features a bi-axial sliding platform for precise 61-key positioning and a ten-link, four-loop robotic hand for key striking. A hierarchical control framework incorporates MIDI-based task mapping, finger optimization using an improved Hungarian algorithm, and impedance–admittance hybrid control for adaptive force–position modulation. An 8-week randomized controlled trial demonstrated that the experimental group significantly outperformed the control group, with a 74.7% increase in Fugl–Meyer scores (50.5 ± 2.5), a 14.6-point improvement in the box and block test (BBT), a 20.2-s reduction in nine-hole peg test (NHPT) time, and a 72.6% increase in rehabilitation motivation scale (RMS) scores (55.4 ± 3.8). The results indicate that combining piano playing with robotic rehabilitation enhances neuroplasticity and engagement, significantly improving motor function, daily activity performance, and rehabilitation adherence. This mechanical-control synergy introduces a new paradigm for music-interactive rehabilitation, with potential applications in home-based remote therapy and multimodal treatment integration.