Background: Investing in mental well-being is considered a supplement to current mental health service delivery in which the treatment and prevention of mental disorders are core components. It may be possible for people to enhance their well-being by boosting their “mental fitness.” Objective: Psyfit, an online, multi-component, fully automated self-help intervention, was developed with the aim of improving well-being and reducing depressive symptoms. The efficacy and cost-effectiveness of this intervention will be examined in a randomized controlled trial. Methods: In this two-armed randomized controlled trial, a total of 290 participants will be assigned to use Psyfit (experimental condition) or to a 6-month waiting list (control condition). Adults with mild to moderate depressive symptoms interested in improving their mental fitness will be recruited from the general population through advertisements on the Internet and in newspapers. Online measurements by self-assessment will be made prior to randomization (pre-test), 2 months after baseline (post-test), and 6 months after baseline (follow-up). Results: The primary outcome is well-being. Secondary outcomes are depressive symptoms, general health, vitality, and economic costs. Analysis will be conducted in accordance with the intention-to-treat principle. Conclusions: This study will examine the efficacy and cost-effectiveness of an online intervention that aims to promote well-being in people with elevated levels of depressive symptoms. If shown to be effective, the intervention could prove to be an affordable and widely accessible intervention to improve well-being in the general population.