Type 2 diabetes mellitus (T2DM) impacts more than 540 million adults worldwide, influenced by insulin resistance and β-cell dysfunction via the dysregulation of AMPK, mTOR, SIRT1, PPARγ, GLP-1, and miRNA pathways. Existing pharmacological treatments offer symptomatic relief; however, they do not thoroughly tackle the underlying molecular mechanisms of the disease. This review consolidates recent evidence regarding phytocompounds that influence these targets, highlighting their multi-targeted therapeutic potential and enhanced safety profiles.

Significant findings indicate that gingerol (Zingiber officinale) promotes a 2-3-fold increase in AMPK phosphorylation and GLUT4 translocation in HepG2 cells; quercetin enhances glucose uptake by upregulating SIRT1/PPARγ; anthocyanins boost GLP-1 secretion; and fucoidan inhibits pathogenic miR-34a-5p, thereby restoring β-cell function. Niazirin, derived from Moringa oleifera, inhibits mTOR to enhance autophagy, whereas curcumin and ginsenoside Rg1 stimulate insulin signalling pathways. Studies conducted both in vitro and in vivo reveal that these compounds surpass single-target synthetics by effectively addressing hyperglycemia, inflammation, and oxidative stress simultaneously. Nanotechnology-enhanced delivery offers the potential for enhanced bioavailability. Prospects encompass precision medicine that integrates genomics, utilises AI for target identification, and modulates the microbiome to enhance personalised management of T2DM. This review article elucidates several key molecular targets in diabetes mellitus that are being addressed for the amelioration of disease severity.