Inflammation is a protective mechanism of the body in response to harmful stimuli. However, persistent inflammation and excessive secretion of inflammatory mediators may lead to chronic inflammation, resulting in dysfunction of cells, tissues, or organs. The vagus nerve isone of the core components in neuro-immune regulation. In recent years, studies have shown that the vagus nerve regulates inflammatory responses, especially anti-inflammatory effects, through multiple pathways, including the cholinergic anti-inflammatory pathway, non-cholinergic anti-inflammatory pathway, and the inflammatory reflex. This review focuses on the core mechanisms underlying the anti-inflammatory effects of the vagus nerve and its clinical applications in autoimmune diseases, infectious diseases, metabolic diseases, and neurological disorders, aiming to provide new insights into clinical anti-inflammatory therapy.