Objectives: The purpose of this study was to compare the functional disability and psychological distress, observed in patents with substance use disorder (SUD) and psychosis. Methods: As a multicenter study, 17 patients with SUD and 49 patients with psychosis, participated in this study. All participants were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) as well as the Kessler Psychological Distress Scale (K10). Results: In patients with SUD, functional disability was observed in approximately 8.5%. In the WHODAS total and all sub-scales scores, patients with SUD showed less severe functional impairment, compared to patients with psychosis. However, psychological distress was more severe in patients with SUD, and was at a very high level. This study confirmed that the psychological distress of patients with SUD, had a significant correlation with functional disability of cognition, interacting with others, and participation. Conclusion: In this study, patients with SUD were identified with distinct clinical features, compared to patients with psychosis.