Abstract: Type 2 diabetes mellitus (T2DM) was identified as the most prevalent form of diabetes. This study employed an integrated strategy combining network pharmacology, metabolomics, and experimental validation to elucidate the therapeutic mechanisms of red mulberry water extract (RMW) in T2DM. Systematic analysis identified six bioactive constituents, with four key components (cyanidin, quercetin, morin, and β-carotene) demonstrating significant interactions with diabetes-related targets. Network pharmacology revealed these compounds modulate critical pathways including AMPK (P=2.3×10⁻⁵), PI3K-Akt (P=1.8×10⁻⁴), and PPAR signaling (P=3.1×10⁻³). In diabetic mice, treatment significantly improved glycemic control (32.5% reduction in fasting glucose, P<0.01), lipid profiles (36.7% lower TG, P<0.05), antioxidant activity (2.1-fold increased SOD, P<0.05), and inflammation (42% reduced TNF-α, P<0.05). Metabolomic analysis further confirmed alterations in catecholamine and lipid metabolism pathways. These findings collectively demonstrate mulberry's multi-target therapeutic potential through synergistic regulation of glucose metabolism, lipid homeostasis, oxidative stress, and inflammatory responses in diabetes.