Objective: The aim of this study was to assess the efficacy of dextrose prolotherapy for treatment of temporomandibular joint (TMJ) hypermobility. Patients and Methods: Twelve patients with bilateral TMJ symptomatic hypermobility were randomly assigned into one of two equal groups. Patients in the active group received four injections of dextrose solution (2ml of dextrose10% and 1ml of 2% mepivacaine) for each TMJ, each six weeks apart, while patients in the placebo group received injections of placebo solution (2ml of saline and 1ml of 2% mepivacaine) using the same schedule. A number of clinical parameters (TMJ pain on palpation, maximal mouth opening (MMO), clicking sound and number of locking during the study periods) were assessed by the same blinded operator at each injection appointments just before injection procedure and three months after the last injection. Results: With the exception of the MMO, there were no statistically significant differences throughout the study intervals between active and placebo groups. By the end of the study, each group showed significant improvement in the TMJ pain on palpation and number of locking and insignificant improvement in clicking sound. The active group showed significant reduction in the MMO at the postoperative 12th week. Differences with baseline mean remained significant at the end of the follow-up period. On the other hand, the placebo group showed insignificant difference in MMO throughout the study periods. At the last 2 intervals, the placebo group showed statistically significant higher MMO means than the active group. By the end of the12th postoperative week, the decrease percentages in MMO were significantly greater in the active group. Conclusion: Prolotherapy using 10% dextrose looks promising for treatment of symptomatic TMJ hypermobility as evident by the therapeutic benefits, simplicity, safety, the patients’ acceptance to the injection technique and the lack of significant side effects. However, continued research into prolotherapy effectiveness in large samples of patient populations with long-term follow-up is needed.