Axis I disorders are one of the major health burdens worldwide. Evidence suggests that Mediterranean diet has key biological factors associated with reducing the progression of these disorders. This systematic review aimed to clarify the relationship between Mediterranean diet and Axis I disorders. PubMed and Scopus databases were searched from January 2016 up to June 2021. Those observational studies in English language that assessed the relationship between Mediterranean diet and Axis I disorders (such as depression, anxiety, eating disorders, schizophrenia, etc.) were included in this review. The Newcastle–Ottawa Scale was used to evaluate the quality of studies. Thirty‐six studies (15 cohorts, 19 cross‐sectional, and 2 case–control) met the inclusion criteria. The results revealed that more than two‐thirds of the studies (25 studies, 69.44%) had significant protective relationship between receiving Mediterranean diet and reducing the symptoms or incidence of Axis I disorders. Most studies were performed on depression (29 studies measured depression at least as one of the Axis I disorders), of which 72.41% reported an inverse relationship. There were also 9 studies on anxiety (studies that measured anxiety at least as one of the Axis I disorders), that 77.77% of them observed protective association. Moreover, majority of the studies (25 studies, 69.44%) had high quality, of which 76% found an inverse relationship. In conclusion, it seems that the Mediterranean diet can reduce the symptoms or the occurrence of Axis I disorders (especially depression and anxiety). However, more extensive review studies, particularly with interventional designs, are necessary to prove the result.