Diabetes, affecting over 10.5% of the global population, leads to severe health complications and economic burdens, highlighting the urgent need for effective therapeutic approaches. Current treatments are often insufficient, prompting the exploration of novel therapeutic agents and delivery mechanisms. This study addresses this gap by investigating the roles of L-arginine (identified as a target drug candidate through network pharmacology) in diabetes management, while also evaluating lipid nanocarriers synthesized from fenugreek seed oil for improved drug delivery. Our docking analyses revealed L-arginine's strong interactions with diabetes-target genes (CYP1A2, CYP2C19, and NFKB), with multiple hydrogen bonds and binding energies ranging from - 7.2 to - 8.9 kcal/mol. Encapsulated L-arginine lipid nanoparticles were characterized using UV-Visible spectroscopy, showing absorbance peaks at 415 nm for simple nanoparticles and 521 nm for L-arginine-loaded nanoparticles. Scanning electron microscopy confirmed an average nanoparticle size of 100.2 nm, and zeta potential analysis indicated a neutral surface charge (- 9.37 mV). Antioxidative activity showed 84.44% inhibition with an IC50 value of 40.5 µg/mL The nanoparticles inhibited albumin denaturation by 81.10% and alpha-amylase by 89.30%, surpassing metformin (78.43% at 1000 µg/mL). Hemolysis percentage was minimal at 10.54%. These findings demonstrate the potential of L-arginine as an anti-diabetic agent and highlight the efficacy of lipid nanocarriers as innovative drug delivery systems, providing a foundation for advancing therapeutic interventions against diabetes.