Temporomandibular joint osteoarthritis (TMJOA) is a painful inflammatory condition that limits mouth opening. Cell-derived exosomes, which have anti-inflammatory effects, are emerging as a treatment for TMJOA. Injection of dental pulp stem cells (DPSCs), which secrete exosomes, can moderate tissue damage in a rat model of TMJOA. However, injected exosomes are quickly cleared, necessitating repeated injections for therapeutic efficacy. Here, vinyl sulfone-modified hyaluronic acid (HA-VS) hydrogels, suitable for encapsulating exosomes are formulated. HA-VS hydrogels degrade in the presence of hyaluronidase and allow for the release of beads of similar size to exosomes over 3 to 6 days. In a rat model of TMJOA, injection of exosomes or exosomes within HA-VS hydrogels significantly attenuated damage-mediated subchondral bone loss as determined by micro-computed tomography, and reduced inflammatory and tissue damage scores as assessed by histology. Overall, DPSCs-derived exosomes attenuated joint damage, but treatment with exosomes within HA-VS hydrogels shows additional protective effects on subchondral bone maintenance and integrity. These findings confirm the protective effects of DPSCs-derived exosomes in moderating tissue damage in TMJOA and suggest that combining exosomes with HA hydrogels can further promote their therapeutic effects.