Trismus is a common symptom in patients with head and neck cancer that affects many aspects of daily life negatively. The aim of this study was to investigate the impact of structured exercise with the jaw-mobilizing device TheraBite on trismus, trismus-related symptomatology, and health-related quality of life (HRQL) in patients with head and neck cancer. Fifteen patients with trismus (maximum interincisal opening [MIO] ≤35 mm) after oncologic treatment for head and neck cancer, underwent a 10-week exercise program with the TheraBite device and were followed regularly. Time between oncologic treatment and start of TheraBite exercise ranged from 0.7 to 14.8 years (average 6.2 years). MIO, trismus-related symptoms, and HRQL was assessed before and after exercise and after 6 months. A significant improvement in MIO was observed post-exercise (3.5 mm, 15.3%, p = 0.0002) and after 6-month of follow-up (4.7 mm, 22.1%, p = 0.0029). A statistically significant correlation was found between increased MIO and fewer trismus-related symptoms. In conclusion, exercise with TheraBite improved MIO and trismus-related symptoms in patients with trismus secondary to head and neck cancer. Structured exercise with the jaw-mobilizing device seems to be beneficial for patients with trismus independent of time since oncologic treatment.