Methyl-CpG binding protein 2 (MeCP2) is a transcription inhibitor that specifically recognizes methylated CpG dinucleotides. MeCP2 is involved in regulating transcriptional activation, regulating chromosome conformation, RNA splicing and other basic life activities, such as embryonic development, tissue differentiation, organ formation, etc. Data shown MeCP2 plays an important role in neuropsychiatric diseases and may also become a new target for the treatment of neuropsychiatric diseases. Therefore, this article reviews the latest progress of MeCP2 in Rett syndrome, depression, addiction, autism and schizophrenia.