Glucose and lipid metabolism disorder is a kind of disease characterized by fat toxicity, glucose toxicity and other pathological manifestations. It is an increasingly popular global public health problem. In view of the limitations of the current treatment methods, it is very meaningful to find new methods to treat metabolic diseases. Metabolic disease is a chronic low-grade tissue inflammation. Macrophages are the main participants in tissue immune homeostasis and inflammatory response. The balance of macrophage polarization breaks and drives inflammatory response and insulin resistance. Janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Notch, Wnt and mitogen-activated protein kinase (MAPK) signaling pathways are involved in this process. Restoring the balance of macrophage polarization is a potential method for treating metabolic diseases. Researchers have found that natural products (NPs) regulate macrophage polarization and improve glucose and lipid metabolism. In this review, based on the existing evidence, we summarized the macrophage lineage and the mediating mechanism of macrophage polarization in glucose and lipid metabolism disorders. Taking obesity, type 2 diabetes, and atherosclerosis as examples, we systematically reviewed the latest progress of plant-derived natural products in improving glucose and lipid metabolism through macrophage polarization. In addition, we also discussed the application of advanced nano-delivery technology in natural products, which can enhance targeting efficiency and therapeutic potential. Finally, we discuss the shortcomings of this field and put forward the view of 'network remodeling'. It is expected to provide reference for clinical treatment and scientific research of glucose and lipid metabolism disorders. • Clarifies the mechanistic links between macrophage polarization and glucose–lipid metabolic dysregulation across key inflammatory and metabolic signaling pathways. • Summarizes how plant-derived natural products regulate macrophage polarization to alleviate obesity, type 2 diabetes, and atherosclerosis. • Evaluates nanodelivery strategies that enhance bioavailability, macrophage targeting, and immunometabolic efficacy while reducing systemic toxicity. • Highlights critical knowledge gaps and proposes macrophage signaling–metabolism reprogramming as a therapeutic concept for glycolipid metabolic disorders.
Li et al. (Fri,) studied this question.