The purpose of this study was to investigate the outcome of a series of consecutive patients with temporomandibular disorder (TMD) who were treated with manual physical therapy interventions and exercise. Consecutive patients with the clinical presentation of TMD completed several self-report measures and underwent a standardized historical and physical examination. Following the examination, patients received a multimodal treatment approach incorporating manual physical therapy and exercise. All self-report questionnaires were completed at a 2-week follow-up. Paired t-tests were performed between the baseline and 2-week follow-up scores. The mean TMD Disability Index scores were 32.1% (15.4%) at baseline and 18.3% (12.5%) at the 2-week follow-up, representing an improvement of 13.9% (CI: 8.2%, 19.5%) (p < 0.05). Patient Specific Functional Scale (PSFS) scores improved 3.1 points (CI: 2.3, 3.9) (p < 0.05). These results suggest that patients with TMD who are treated with a rehabilitation program including manual physical therapy interventions plus exercise, with or without iontophoresis with dexamethasone, can demonstrate clinically meaningful improvements in disability and overall perceived change in a relatively short period of time.