The decline of cognitive function caused by aging and neurological diseases seriously decreases the ability of daily life and the quality of life in old people. Therefore, it has been paid more and more attention to find effective interventions to improve the cognitive function and quality of life of the old people. Exercise can reduce the risks of Alzheimer disease (AD) and depression, improve the memory and cognitive function, and keep brain healthy, but the underlying molecular mechanism remains unclear. Irisin is a muscle cytokine, which is a cleaved version of fibronectin type Ⅲ domain-containing protein 5 (FNDC5), and the exercise is the main factor to promote the synthesis and secretion of irisin. Irisin can promote the differentiation of neural stem cells, increase the neuroplasticity, and improve the memory and cognitive function. Recent studies have shown that exercise can directly promote the expression of FNDC5 in nerve tissue, and influence the microstructure and function of the brain by peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-FNDC5-brain-derived neurotrophic factor (BDNF) pathway. Exercise can also stimulate the muscles and other tissues to synthesize and secrete a large amount of irisin, and promote the brain to secrete BDNF. In view of the important role of irisin in the regulation of nervous system and its close relationship with exercise, this paper reviews the research progress in the mechanism of irisin regulating exercise to promote the brain function.