A novel oral insulin nanocarrier was developed using silver sulfide quantum dots (Ag₂S QDs) conjugated with insulin and coated with a pH- and enzyme-sensitive chitosan/glucose (CS/GS) polymer. This formulation is insoluble in acidic environments and becomes soluble at neutral pH, enabling controlled release of insulin in response to glucosidase enzymes. The formulation was shown to target the liver in mice and rats, reducing blood glucose levels without causing hypoglycaemia or weight gain in diabetic animals. Non-diabetic baboons also exhibited reduced blood glucose levels without adverse effects. The formulation demonstrated no toxicity in mice, rats, or non-human primates. The nanocarrier showed enhanced intestinal uptake in human duodenum explants and increased fat storage in Caenorhabditis elegans. In mice and rats, the formulation provided dose-dependent glucose control with no hypoglycaemia, and in non-diabetic baboons, it reduced blood glucose levels without causing hypoglycaemia. The study highlights the potential of this nanocarrier for oral insulin delivery, offering a safer and more effective alternative to injectable insulin. The formulation is designed for broader applications in oral peptide delivery, including liver-targeted therapies and organ-specific treatments. The research provides a foundation for further clinical investigations and highlights the importance of developing insulin delivery systems that minimize hypoglycaemic episodes and improve patient outcomes.A novel oral insulin nanocarrier was developed using silver sulfide quantum dots (Ag₂S QDs) conjugated with insulin and coated with a pH- and enzyme-sensitive chitosan/glucose (CS/GS) polymer. This formulation is insoluble in acidic environments and becomes soluble at neutral pH, enabling controlled release of insulin in response to glucosidase enzymes. The formulation was shown to target the liver in mice and rats, reducing blood glucose levels without causing hypoglycaemia or weight gain in diabetic animals. Non-diabetic baboons also exhibited reduced blood glucose levels without adverse effects. The formulation demonstrated no toxicity in mice, rats, or non-human primates. The nanocarrier showed enhanced intestinal uptake in human duodenum explants and increased fat storage in Caenorhabditis elegans. In mice and rats, the formulation provided dose-dependent glucose control with no hypoglycaemia, and in non-diabetic baboons, it reduced blood glucose levels without causing hypoglycaemia. The study highlights the potential of this nanocarrier for oral insulin delivery, offering a safer and more effective alternative to injectable insulin. The formulation is designed for broader applications in oral peptide delivery, including liver-targeted therapies and organ-specific treatments. The research provides a foundation for further clinical investigations and highlights the importance of developing insulin delivery systems that minimize hypoglycaemic episodes and improve patient outcomes.