N6-methyladenosine (m6A), which belongs to the field of the epigenetic modifications, is a common and reversible mRNA modification in eukaryotic RNA. Regulated by methyltransferases, demethyltransferases, and reader proteins, m6A modification affects the expression of relevant proteins by mediating RNA transcription, splicing, translation, and other processes, thereby regulating the physiological and biochemical processes of the organism. Major depressive disorder (MDD), characterized by a high incidence, low cure rate, and a high recurrence rate, is a psychiatric disorder with multiple etiological factors, including genetic factors, environmental factors and epigenetic factors. However, the specific mechanisms underlying MDD remain unclear. Recent studies have found a close relationship between m6A modification and the pathogenesis of MDD, making it a hot topic in MDD research. This article reviews the m6A methylation, as well as the expression and roles of related enzymes in the central nervous system of MDD patients, aiming to provide new insights and potential drug targets for the research and treatment of MDD.