The public health issue of glucolipid metabolic disorders (GLMD) has grown significantly, posing a grave threat to human wellness. Its prevalence is rising yearly and tends to affect younger people. Metaflammation is an important mechanism regulating body metabolism. Through a complicated multi-organ crosstalk network involving numerous signaling pathways such as NLRP3/caspase-1/IL-1, NF-B, p38 MAPK, IL-6/STAT3, and PI3K/AKT, it influences systemic metabolic regulation. Numerous inflammatory mediators are essential for preserving metabolic balance, but more research is needed to determine how they contribute to the co-morbidities of numerous metabolic diseases. Whether controlling the inflammatory response can influence the progression of GLMD determines the therapeutic strategy for such diseases. This review thoroughly examines the role of metaflammation in GLMD and combs the research progress of related therapeutic approaches, including inflammatory factor-targeting drugs, traditional Chinese medicine (TCM), and exercise therapy. Multiple metabolic diseases, including diabetes, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, and others, respond therapeutically to anti-inflammatory therapy on the whole. Moreover, we emphasize the value and open question of anti-inflammatory-based means for treating GLMD. Display omitted •Metaflammation has a crucial role in regulating Glucolipid metabolic disorders (GLMD).•Inflammation-associated signaling pathways influence the development of multiple metabolic diseases.•The role of inflammatory mediators in the co-morbidity of multiple metabolic diseases needs to be further investigated.•Anti-inflammatory treatment shows an overall therapeutic effect on multiple metabolic diseases simultaneously.