BACKGROUND: Mental health disorders still rank as leading causes of morbidity worldwide despite increasing awareness and improvements in treatment. Notably, low- and middle-income countries like Uganda, are disproportionately affected by such disorders. The burden of depressive symptoms in these countries is particularly high among students, aggravated by poverty, malnutrition, and inadequate public health governance, yet it is clearly under-researched, making it hard to achieve several of UN Sustainability Development Goals. Current treatment options are insufficient to tackle the increased burden of depressive disease. This is more challenging for low-resource regions especially in Sub-Saharan Africa, suggesting the need for alternative treatments that can swiftly be applied if proven effective. The main aim of this randomized controlled trial (RCT) is therefore to examine if a low-cost healthy diet (based on local Ugandan foods) combined with easy-to access mindfulness cognitive therapy can reduce depressive symptoms among university students in Uganda. METHODS: We will recruit female and male students at Makerere University, the largest public university in Uganda, to an open, intention-to-treat, two-armed RCT. Those who score above a predefined threshold on a self-reported assessment of depressive symptoms, measured by the Center for Epidemiological Studies - Depression score (CES-D), are eligible for study inclusion and will be randomized to either an intervention (n = 125) or a control (n = 125) group. The intervention group will receive educational group-based sessions on how to prepare a Mediterranean-type of healthy diet and how to adhere to the principles of mindfulness-based cognitive therapy. Outcome measures include self-reported depression symptoms, quality of life, and dietary intakes. In addition we will perform a cost-effectiveness analysis. The RCT intervention will last 9 months, followed by additional 15 months with regular data collections. DISCUSSION: We here describe a novel approach to treat depressive symptoms among university students living in resource constraint settings, by combining a healthy diet with low threshold psychotherapy. If this intervention succeeds, our project can be viewed as a step towards evidence-based behavior practices for young adults with a common mental disorder (depression) that are beneficial to public mental health initiatives and management. TRIAL REGISTRATION: The RCT is registered in ClinicalTrials.gov (ID: NCT05848973). The date of registration was August 14, 2023.