SUMMARY OBJECTIVE Body mass index (BMI) values of 25 kg/m2 or more have been associated with poor cognitive outcomes, reduced health-related quality of life (HRQoL), and mental health disorders. Participating in regular exercise may improve these negative outcomes. However, the optimal exercise prescription remains to be clarified. The purpose of the present study is to compare the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on HRQoL, depression, and anxiety levels in middle-aged overweight men. METHODS Twenty-five sedentary, overweight men participated in the 8-week training intervention. Subjects were randomized into MICT or HIIT and performed exercise sessions three times per week for 8 weeks. Participants answered the Physical Activity Readiness Questionnaire, the Short Form-36 survey, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Statistical analysis was carried out using the GraphPad Prism 7.0, and the level of significance was set at 5% to quantitative variables. RESULTS HRQoL scores were enhanced to all domains of both the groups. MICT and HIIT did not significantly change the depression levels in middle-aged overweight men (p>0.05). Nevertheless, MICT was capable to reduce the anxiety levels in middle-aged overweight men (p<0.05). However, there was not a significant change in the anxiety levels at the HIIT group. CONCLUSIONS HIIT may be a useful treatment to improve the HRQoL, but MICT alone can positively impact the anxiety levels in middle-aged overweight men.