Background: There has been considerable interest in Japanese society in the problem of work-related stress leading to depressive symptoms, and an increasing number of primary houseworkers maintain paid employment. The purpose of this study was to examine the differential impact of multiple roles associated with psychological distress among Japanese workers. Methods: We studied 722 men and women aged 18–83 years in a cross-sectional study. The K10 questionnaire was used to examine psychological distress. Results: The proportion of participants with psychological distress was higher in women (17.8%) compared with men (11.5%). Having three roles significantly decreased the risk of psychological distress [women: odds ratio (OR), 0.37-fold; men: OR, 0.41] compared with only one role. In working married women, there was significantly less psychological distress (OR, 0.27), and those with childrearing or caregiving responsibilities for elderly parents had significantly less psychological distress (OR, 0.38) than those with only an employment role. Similarly, working married men who had childrearing or caregiving responsibilities for elderly parents had significantly less psychological distress (OR, 0.41) than those who had only an employment role. Conclusion: The present study demonstrated that participants who had only an employment role had an increased risk of psychological distress. The degree of psychological distress was not determined solely by the number of roles. It is important to have balance between work and family life to reduce role conflict and/or role submersion, which in turn may reduce the risk of psychological distress.