Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.