The study aimed to compare the efficacy of platelet-rich plasma (PRP) injections for the treatment of temporomandibular joint osteoarthritis (TMJ-OA) with hyaluronic acid (HA) therapy. This randomized controlled trial included 70 patients with TMJ-OA, randomly divided into either a PRP or HA group. The pain intensity, maximum mouth opening (MMO), TMJ sound score, and proportion of crepitus were recorded and compared at baseline and at 1, 3, and 6 months. Both groups showed statistically significant improvements in pain intensity, MMO, TMJ sound, and scale scores during the 6-month follow-up period. The improvements in pain intensity during mouth opening at 1 month, MMO at 1, 3, and 6 months, TMJ sound score at 1 and 3 months, and GAD-7 score at 6 months in the PRP group were greater than in the HA group (p < 0.05). Compared with the HA group, imaging improvement in the PRP group was also higher (p < 0.05). Within the limitations of the study it seems that the application of PRP therapy in TMJ-OA is should be considered whenever possible.