Customization of mental health therapies needs to consider the differences in degree of brain maturity between young (18–29 years) and mature (30 years or older) adults as well as brain morphology among men and women. The aim of this study was to identify the significant dietary and lifestyle contributors to mental distress in these sub-populations. Independent repeated cross-sectional sampling was performed for over a 5-year period (2014–2019) to collect data from different populations at different time-points and seasons. A backward stepwise regression analysis was used on 2628 records. Mental distress in young women was associated with high consumption of caffeine and fast-food, and it was negatively correlated with moderate-high levels of exercise as well as frequent breakfast consumption. Mature women shared several common factors with young women; however, high fruit consumption was negatively associated with mental distress. For young men, high exercise, moderate consumption of dairy, and moderate-high intake of meat were negatively associated with mental distress. In addition, high fast-food and caffeine consumption were positively associated with mental distress in young men. For mature men, strong negative associations between higher education, moderate intake of nuts and mental distress surfaced. Our results support the need to customize dietary and lifestyle recommendations to improve mental wellbeing.