Type 2 diabetes mellitus (T2DM), a globally prevalent chronic metabolic disorder, imposes a significant worldwide public health burden. As a vital "microbial organ" within the human body, the balance of the gut microbiota (GM) structure and function is crucial for maintaining host metabolic health. Short-chain fatty acids (SCFAs), the metabolic products of GM, serve as key signaling molecules that play central roles in maintaining intestinal homeostasis, regulating systemic energy metabolism, and improving insulin sensitivity. Dysregulation of the "GM-SCFA axis" has emerged as a core pathological mechanism in the onset and progression of T2DM. Traditional Chinese Medicine (TCM) possesses unique advantages in T2DM treatment through its "holistic regulation and multi-targeted intervention," which enables precise modulation of the GM-SCFA axis. This paper provides a systematic review of the pathological mechanisms by which dysregulation of the GM-SCFA axis induces T2DM, and specifically covers energy metabolism disorders, insulin resistance, intestinal barrier impairment, chronic low-grade inflammatory activation, abnormal bile acid metabolism regulation, and disrupted gut-pancreatic axis and gut-brain axis signaling. Using keywords such as TCM, GM, SCFAs, and T2DM, we conducted an extensive literature search across databases including PubMed, Google Scholar, and Web of Science for publications from the past decade. This systematic review examines the application of TCM in regulating the "GM-SCFA axis" from multiple perspectives: Chinese herbal compounds (e.g., Zuogui Jiangtang Qinggan Formula, Gegen Qinlian Decoction), Chinese patent medicines (e.g., Shouhui Tongbian Capsules, Compound Danshen Dripping Pills), single-herb Chinese medicines (e.g., Edgeworthia gardneri, Alpinia oxyphylla), single-component compounds from TCM (e.g., Cyclocarya paliurus polysaccharide, Achyranthes bidentata polysaccharide water-soluble 1), and other TCM therapies (e.g., tuina, acupuncture). This study aims to systematically explore the mechanisms by which dysregulation of the "GM-SCFA axis" induces T2DM while providing novel therapeutic strategies for T2DM prevention and treatment using TCM. It also seeks to establish scientific foundations for developing novel TCM intervention strategies targeting the "GM-SCFA axis" in T2DM management.
