Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we evaluated silver sulfide quantum dots (QDs) with a chitosan/glucose (CS/GS) encapsulating polymer to produce an oral insulin nanocarrier (QD-INS-CS/GS). This formulation was insoluble at acidic-neutral pH, showed increased absorption in human duodenum explants and Caenorhabditis elegans; and was highly sensitive to glucosidase enzymes to mediate hepatic release. In C57BL/6J mice, 50% of QD-INS-CS/GS distributed to the liver and promoted a dose-dependent reduction in blood glucose. Compared to injectable insulin, QD-INS-CS/GS had a similar effect size and time-to-onset in non-obese diabetic mice and streptozotocin-induced diabetic rats without promoting hypoglycaemia or weight gain. Non-diabetic baboons showed a dose dependent-reduction in blood glucose up to 30% with 10 IU/kg in insulin tolerance testing. No biochemical or haematological toxicity, or adverse events were observed. These studies demonstrate the successful application of this oral insulin platform with inhibited hypoglycaemia.