Obesity-associated chronic low-grade inflammation is a major driver of metabolic disorders in the body, which is involved in the onset and progression of metabolic diseases such as metabolic syndrome and insulin resistance, and for which there is currently no effective treatment, an important reason being that the mechanisms of inflammation regulation are not fully understood. Vagal-mediated cholinergic signaling can improve obesity-related inflammation by regulating the body's metabolic homeostasis and immune function. Recent studies have shown that the imbalance between the pro-inflammatory and anti-inflammatory systems due to the impairment of the cholinergic anti-inflammatory pathway, which is the basic anti-inflammatory pathway in obesity, is the key to developing inflammation. Metformin (MF) is a clinically useful hypoglycaemic drug whose mechanism of action has been elucidated to control inflammation and improve metabolic disorders. It has been found that MF exerts synergistic effects with the activation of cholinergic signaling pathways in the body, and there may be an important link between the two, which makes it possible for MF to exert its effects by targeting cholinergic anti-inflammatory pathways. In this paper, we would like to review the high-fat diet-induced impairment of cholinergic anti-inflammatory pathways and the possible mechanisms of MF targeting cholinergic anti-inflammatory pathways, to provid new insights for the prevention and treatment of obesity-driven inflammatory and metabolic diseases.