Perioperative neurocognitive disorders (PND) are common complications related to anesthesia and surgery, especially in elderly patients. Glial cell line‑derived neurotrophic factor (GDNF) is widely distributed throughout the brain, exhibiting trophic effects on dopaminergic neurons and other types of neurons. It has been shown to play a potential therapeutic role in various neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease, etc. It also improves spatial learning and memory ability and ameliorates the symptoms of PND. This paper reviews that GDNF is involved in the development of PND through multiple pathways including protecting hippocampal neurons, activating a variety of survival signaling pathways via binding its specific receptors, affecting synaptic plasticity, reducing neuroinflammation, etc, so as to provide a new direction for exploring the pathogenesis and prevention and treatment of PND.