Mulberry Leaf-Derived Bioactive Constituents on Diabetes: Structure, Extraction, Quality Analysis, and Hypoglycemic Mechanisms

(1) Background: Diabetes mellitus is a chronic metabolic disease with a rising global prevalence. Mulberry leaf (ML), a traditional medicinal and edible plant, possesses notable hypoglycemic effects and has a long history of usage. This review aims to systematically consolidate the research progress on the hypoglycemic constituents derived from ML, including their chemical structure, extraction methods, quality analysis techniques, and hypoglycemic mechanisms. (2) Methods: Adhering to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines, a comprehensive literature search was conducted using Web of Science and PubMed databases to find relevant studies published between 2015 and 2025. (3) Results: This review evaluates both conventional and modern techniques such as water extraction, ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzyme-assisted extraction (EAE), highlighting their advantages and limitations when applied on ML. Additionally, this review examines the analytical techniques applied in the quality control of ML and its constituents. This is complemented by a summary of hypoglycemic mechanisms, focusing on the inhibition of oxidative stress, amelioration of insulin resistance, regulation of related enzyme activity, and modulation of gut microbiota. (4) Conclusions: ML demonstrates considerable potential for treating diabetes. However, further studies are needed for new drug discovery based on new ML-derived bioactive constituents, highly efficient extraction methods, quality analysis techniques, and underlying mechanisms.