Abstract

Diabetes mellitus represents one of the most significant global public health challenges of the twenty-first century, with an estimated 537 million adults currently affected worldwide and projections indicating a dramatic rise in disease burden over the coming decades. Despite substantial pharmacological advances, existing therapeutic regimens—including metformin, sulfonylureas, thiazolidinediones, and sodium-glucose cotransporter-2 (SGLT2) inhibitors—remain limited by adverse effect profiles, inadequate glycaemic control in a proportion of patients, and the progressive nature of the underlying disease. Plant-derived compounds have attracted considerable scientific interest as potential sources of novel antidiabetic agents owing to their structural diversity, multi-target pharmacological properties, and extensive ethnobotanical history. This article provides a comprehensive review of the major classes of phytochemicals—including flavonoids, alkaloids, terpenoids, glycosides, and polyphenols—that have demonstrated antidiabetic activity, with emphasis on their biochemical mechanisms of action. These mechanisms encompass enhancement of insulin receptor signalling, inhibition of carbohydrate-digesting enzymes, upregulation of glucose transporters, activation of AMP-activated protein kinase (AMPK), and attenuation of oxidative stress and systemic inflammation. The article further examines preclinical and clinical evidence supporting their therapeutic potential, challenges in pharmacokinetic optimisation and standardisation, recent advances in drug delivery systems, and regulatory considerations in the translation of plant-based molecules into approved pharmaceuticals. It is argued that a rigorous, mechanism-driven approach to the investigation of phytochemicals offers a promising pathway for the development of safer and more effective antidiabetic therapies.