With the internal volar locking plate (VLP) technique emerging as a preferred surgical approach, early post-surgery therapeutic exercises have shown promise in promoting wrist functionality after distal radial fractures (DRFs). The biomechanical microenvironment, particularly the role of biomechanical stimuli, plays a crucial role in guiding stem tissue formation at the fracture site. However, much less is known about how various hand exercises interact with the microenvironment and influence fracture healing outcomes. This study employed the Leap Motion Controller for markerless hand motion capture and utilised an enhanced OpenSim hand model to simulate these motions. An advanced DRF healing model, integrating angiogenesis and the mechano-regulated maturation of callus tissue, was applied to simulate the MSCs differentiation and predict the healing outcomes. The effects of various rehabilitation exercises on DRFs’ healing outcomes were systematically analysed. The results showed rehabilitation exercises, such as wrist extension/flexion and ulnar deviation, generally had a higher contact force on the distal radius compared with the slack state. Also, the relationship between contact force and muscle activations was not always linear, reflecting the intricate dynamics of the kinematic system. Exercise could induce changes in the bony bridge and cartilage formation, while angiogenesis remained unaffected. In the initial weeks, gripping exercises proved most beneficial, but as time progressed, extension and flexion exercises became more advantageous. The study highlights the importance of tailoring rehabilitation exercises to the dynamic healing process of DRFs. As the healing trajectory progresses, the therapeutic efficacy of specific exercises evolves, necessitating adaptive and patient-specific rehabilitation programs.