Brain diseases, including neurodegenerative, cerebrovascular and neuropsychiatric diseases, have posed a deleterious threat to human health and brought a great burden to society and the healthcare system. With the development of medical technology, vagus nerve stimulation (VNS) has been approved by the Food and Drug Administration (FDA) as an alternative treatment for refractory epilepsy, refractory depression, cluster headaches, and migraines. Furthermore, current evidence showed promising results towards the treatment of more brain diseases, such as Parkinson's disease (PD), autistic spectrum disorder (ASD), traumatic brain injury (TBI), and stroke. Nonetheless, the biological mechanisms underlying the beneficial effects of VNS in brain diseases remain only partially elucidated. This review aims to delve into the relevant preclinical and clinical studies and update the progress of VNS applications and its potential mechanisms underlying the biological effects in brain diseases.