Depression is a common mental disorder and a leading cause of global disease burden. Emerging evidence supports diet as an adjunct treatment for depression. Previous studies are limited, meaning it is unclear whether improvements are directly due to dietary change. The Optimising Nutritional Psychiatry Treatment: Investigating the Mediterranean Diet to Improve Symptoms of Major Depressive Disorder (OPTIMISM) trial aims to address this gap through a sham-controlled randomised feeding trial design. The OPTIMISM trial is a 4-week double-blind, sham-controlled, randomised feeding trial. A total of forty-four participants with major depressive disorder in a current major depressive episode of moderate to severe severity will be recruited and randomised to a Mediterranean or a sham control diet, designed to reflect typical dietary intake of the general population. All food will be provided for 4 weeks. Participants will complete assessments and have blood and stool collected at baseline and 4 weeks. The primary outcome is the differential change in clinician-rated depressive severity at 4 weeks. Exploratory outcomes include patient-rated depressive and anxiety symptoms and quality of life. Potential mechanisms will be evaluated through analysis of biological samples. An additional group of twenty-two healthy individuals without depression will also be recruited and will receive a Mediterranean diet for 4 weeks; their data will determine whether clinical and biological responses to the intervention are unique to depression and whether the diet treatment modulates depression-related pathology. If the intervention diet leads to a greater reduction in depressive symptoms compared with a sham control diet, this trial will provide preliminary evidence supporting the use of a Mediterranean diet in the treatment of depression.