Mental disorders are a category of mental problems with diagnostic significance, characterized by changes in cognition, emotion, and behavior, and may be accompanied by painful experience or functional impairment. From the perspective of neurobiochemical abnormalities, the “glutamate hypothesis”suggests that glutamate dysfunction in the central nervous system can induce mental disorders, including abnormalities in the genes encoding glutamate AMPA receptor. The GRIA2 gene encodes the GluR2 subunit of AMPA receptor, and it has been studied as a susceptibility gene for various mental disorders in recent years, with inconsistent results. Herein, we reviewed the research progress on the association of GRIA2 polymorphism with mental disorders such as schizophrenia, major depression, and bipolar disorder, among others, as well as response to antipsychotic drugs in recent years.