World Health Organization projections estimate that worldwide approximately one-third of adults are overweight and one-tenth are obese. There is accumulating research into the Mediterranean diet and whether it could prevent or treat obesity. Therefore, the purpose of this paper was to systematically review and analyse the epidemiological evidence on the Mediterranean diet and overweight/obesity. We identified 21 epidemiological studies that explored the relationship between the Mediterranean diet and weight. These included seven cross-sectional, three cohort and 11 intervention studies. Of these, 13 studies reported that Mediterranean diet adherence was significantly related to less overweight/obesity or more weight loss. Eight studies found no evidence of this association. Exploring the relationship between the Mediterranean diet and overweight/obesity is complex, and there are important methodological differences and limitations in the studies that make it difficult to compare results. Although the results are inconsistent, the evidence points towards a possible role of the Mediterranean diet in preventing overweight/obesity, and physiological mechanisms can explain this protective effect. Despite this, more research is needed to substantiate this association. Epidemiological studies should use a consistent universal definition of the Mediterranean diet, and address common methodological limitations to strengthen the quality of research in this area.