Background: Anterior disc displacement without reduction (ADDWOR) is one of the most annoying temporomandibular disorders (TMDs). Several medications have been used for intra-articular injection in temporomandibular joint (TMJ) for treatment of ADDWOR. One of the widely used medications is Hyaluronic acid (HA) due to its biological functions inside body joints. Botox also has a very crucial role for pain relief in joints and has never been intra-articularly injected for treatment of any TMD. Aim: To compare the intra-articular injection of HA-Botox mixture versus HA alone for the treatment of Anterior disc displacement of TMJ. Methods: 28 patients seeking treatment of ADDWOR were randomly divided into two groups, group I injected with HA-Botox mixture, while group II injected with HA only. The two groups were evaluated at 1 week, 1 and 3 months post-operatively. Results: A significant difference was found between the two groups in any of the evaluation variables. At the end of the treatment, a general improvement of the clinical status was noticed; MRI, however, showed some degrees of condyle–disc incoordination in some patients. Conclusion: Addition of Botox to Hyaluronic acid in intra-articular injection of TMJ has a significant improvement in the treatment of ADDWOR.