Objective: The effects of lifestyle interventions on the prevention of a decline in work ability and mental health are not well known. The aim of this randomized controlled trial was to examine the effects of healthy lifestyle changes on work ability, sleep, and mental health. Methods: Workers aged 18–65 years, who were free from cardiovascular diseases, diabetes, and malignant diseases, and did not use medication for obesity or lipids were included (N = 319). Based on their cholesterol balance, participants were classified into medium-risk and high-risk groups and were randomized into four arms: group lifestyle coaching (N = 107), individual lifestyle coaching (N = 53), the control group for group coaching (N = 106), and the control group for individual coaching (N = 53). The intervention groups received eight sessions of mostly remote coaching for 8 weeks about healthy diet, physical activity, other lifestyle habits, and sources/management of stress and sleep problems, and the control groups received no intervention. In individual coaching, the coach focused more on individual problem solving and the possibilities for motivation and change. The intention-to-treat principle was applied, and missing data on the outcomes were imputed using multiple imputation. Results: After the completion of the intervention, the risk of depressive symptoms was lower by 53% (95% CI 1–77%) in participants who received individual lifestyle coaching compared with the control group. The intervention had no beneficial effects on anxiety, work ability, sleep duration, or daily stress. In subgroup analyses, group lifestyle coaching had beneficial effects on depressive symptoms and work ability in participants with less tight schedules or less stretching work, whereas individual lifestyle coaching lowered the risk of depressive symptoms in those with fewer overlapping jobs, less tight schedules, or less stretching work. Conclusion: Short but intensive remote lifestyle coaching can reduce depressive symptoms and improve work ability, and time-related resources at work may improve mental health in the context of individual lifestyle intervention. However, further randomized controlled trials are needed to confirm the findings.