Abstract: Cognitive dysfunction often occurs in Alzheimer’s disease, Parkinson’s disease, cerebrovascular disease, or other neurodegenerative diseases, and can significantly impact the quality of life of patients and create serious social, psychological, and economic burdens for individuals and their families. Numerous studies have confirmed that exercise can slow down the decline in cognitive function through multiple pathways, in which FNDC5 plays an important role. However, the current research on the modulation of FNDC5 by exercise and its improvement of hippocampal cognitive function lacks a systematic and comprehensive understanding. Therefore, this article focuses on the latest research progress regarding the role of exercise-induced FNDC5 in cognitive function, systematically reviews the positive effects of FNDC5 on cognitive function impairment caused by various factors, and clarifies the specific mechanisms by which exercise-induced FNDC5 improves cognitive function by inhibiting neuroinflammation and improving hippocampal neurogenesis and hippocampal synaptic plasticity. Based on the existing literature, we also identify the areas that require further research in this field. Overall, this article provides a theoretical basis for the exercise-based prevention and improvement of cognitive function impairment.