The aim of this cross-sectional study was the evaluation of the oral health-related quality of life (OHRQoL) in patients with depression or attention-deficit/hyperactivity disorder (ADHD) in comparison with a group of mentally healthy individuals. Patients from the Department of Psychiatry and Psychotherapy, University of Leipzig, Germany, were recruited. A healthy comparison group (HC) was recruited from the Department of Cariology, Endodontology and Periodontology. The OHRQoL was assessed using the Oral Health Impact Profile G14 (OHIP G14). Furthermore, a questionnaire regarding oral hygiene behaviour was applied. A total of 141 patients with depression or ADHD (depression n = 94, ADHD n = 47) and 145 HC individuals with a balanced age and gender distribution were surveyed. OHIP G14 median scores were significantly higher in the overall psychiatric patient group compared to HC (5.00 vs. 0.00, < 0.001). This was also found for the four dimensions of OHIP G14 ( < 0.001). The OHIP G14 sum score of patients with depression and ADHD was comparable (5.00 vs. 6.50, = 0.302). A significant association among psychiatric patients between smoking, gum bleeding, professional tooth cleaning, oral health education, interdental cleaning, and elevated OHIP scores was found ( < 0.001). In conclusion, patients with depression and adults with ADHD show a reduced OHRQoL. A contradictory association between oral hygiene/oral health behaviour and OHRQoL supports the hypothesis of a changed perception of oral conditions in patients with mental diseases. Interdisciplinary collaboration between psychiatric specialists and dentists should be fostered.