Abstract

Obesity and type 2 diabetes mellitus (T2DM) are tightly interlinked metabolic disorders characterized by insulin 
resistance, chronic low-grade inflammation, and dysregulated energy homeostasis. Together they form a 
convergent pathophysiological entity often termed “diabesity.” Mounting evidence implicates dietary 
polyphenols diverse phytochemicals found in fruits, vegetables, teas, cocoa, whole grains, herbs, and spices as 
promising multi-target modulators of diabesity. This review synthesizes current knowledge on the chemical 
classes of polyphenols and integrates mechanistic insights spanning appetite regulation, digestive enzyme 
inhibition, adipogenesis and lipolysis, browning/thermogenesis, insulin signaling, incretin biology, hepatic 
glucose and lipid metabolism, gut microbiota remodeling, antioxidative and anti-inflammatory pathways, 
endothelial function, and β-cell protection. We discuss pharmacokinetics and bioavailability challenges 
(including the pivotal role of the microbiome), safety considerations, clinical evidence to date, and translational 
strategies such as synergistic combinations, food design, and novel delivery systems. Finally, we outline research 
gaps and pragmatic recommendations for leveraging polyphenols as adjuncts to lifestyle therapy and standard 
pharmacotherapy for obesity and T2DM. 
Keywords: polyphenols; diabesity; insulin resistance; AMPK; gut microbiota