To assess the efficacy of dextrose prolotherapy on the clinical signs and symptoms of patients having disc displacement with reduction (DDWR). This prospective, randomized, double-blind clinical study included thirty patients suffering from bilateral DDWR. The patients were randomly divided into two equal groups. After induction of local anesthesia, each joint was injected in two sites; one in the superior joint space and the other in the retrodiscal tissue, using 25% dextrose solution in group I and normal saline in group II. Pain intensity, maximal interincisal opening (MIO), and joint sounds (JS) were evaluated preoperatively, 1 week after each injection, and 3 months and 6 months after the last injection. Patients in group I showed significant improvement in pain and MIO, and higher satisfaction with treatment than patients in group II. Compared to saline injection, dextrose injection resulted in an improvement in JS but without significant difference within and between groups. Intra-articular injection of 25% dextrose is effective in the treatment of pain and dysfunction of TMJ DDWR as shown by significant improvement in pain and MIO and patient satisfaction. The technique is simple, easy to do, safe and should be adopted whenever appropriate.