The N-methyl-D-aspartic acid （NMDA） receptors are abundant in the hippocampus. NMDA receptors mediate long-term potentiation （LTP） and long-term depression （LTD）， both of which are closely related to cognition. Activation of NMDA receptors may exert both neuroprotective and neurotoxic effects depending on two models， the localization models and the subunit composition models. However， models can only give a relatively macroscopic overview of the different effects induced by activation of NMDA receptors， and the changes in NMDA receptors are unique in different diseases. Therefore， in this paper， Parkinson disease （PD）， Alzheimer disease （AD）， schizophrenia and anti-NMDA receptors encephalitis are taken as examples to explore the alterations of hippocampal NMDA receptors in cognitive impairment in different diseases， and regulating the function of hippocampal NMDA receptors subunits is suggested as a potential target for the treatment of cognitive impairment.