Histone deacetylase 3 （HDAC3） is an epigenetic negative regulatory factor associated with cognitive impairment， widely expressed in the amygdala， hippocampus， and cortex. The activated HDAC3 has neurotoxic effects and negatively regulates the formation of cognition and memory. This paper reviews the mechanism of HDAC3 in cognitive impairment and explores the development prospects of HDAC3 inhibitor therapy.