With the introduction and implementation of China’ s three-child policy, the productivity of elderly mothers in China has increased yearly. Advanced elderly mothers is prone to a variety of difficult and high-risk conditions during pregnancy and delivery, with a subsequent increase in the birth rate of high-risk neonates. High-risk neonates are treated and cared for in the neonatal intensive care unit after birth and separated from their mothers. Maternal separation impairs cognitive functions, but no effective care has been found in clinical care. Numerous animal experiments have shown that enriched environment can improve cognitive dysfunction caused by diseases such as alzheimer's disease, depression, and ischemic stroke, but there are few reports and disagreements about the role and mechanism of the enriched environment in the model of maternal separation. Therefore, we reviewed the research progress on the effects of an enriched environment on cognitive functions in rodent models of maternal separation and the mechanisms of action with oxidative stress, epigenetics, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis to provide new ideas for the improvement and care of cognitive functions in high-risk neonates.