Introduction: Myofascial pain dysfunction syndrome (MPDS) is a common presenting condition in the dental office. No specific therapy has proven its superiority over the other in managing myofascial pain dysfunction syndrome. Since phonophoresis was beneficial for other musculoskeletal medical conditions, the same strategy was adopted to prove its efficacy in MPDS. Aim and Objective: The aim of the study is to compare and evaluate the effectiveness of therapeutic ultrasound (ThUS) and diclofenac and thiocolchicoside gel phonophoresis in MPDS. Materials and Methods: Thirty patients with MPDS were randomly assigned into two groups. Group 1 (n = 15), therapeutic ultrasound was applied with ultrasound gel without any therapeutic ingredient for 10 min and five sessions. Group 2 (n = 15), ultrasound was applied with ultrasound gel with diclofenac and thiocolchicoside gel for 10 minutes and five sessions. Pain and mouth opening was taken as evaluation parameters. Result: A comparison of results obtained from the two groups before and after treatment at the end of each session shows significant improvement in both the parameters. However, in Group 2 more improvement in all outcome variables can be seen compared with group 1. Conclusion: Phonophoresis with diclofenac and thiocolchicoside (analgesic and muscle relaxant) proved to be an excellent treatment in MPDS. They proved more effective than therapeutic ultrasound in controlling pain and improving mouth opening.