Insulin has been widely used as a peptide drug to treat both type 1 and type 2 diabetes mellitus by promoting the absorption of glucose from the blood into the liver, fat, and skeletal muscle cells. While it is usually administered via subcutaneous injections, excessive injections could lead to non-compliance by patients owing to injection pain and associated side effects, including trypanophobia, lipodystrophy, and peripheral hyperinsulinemia . As such, there has been a growing interest in the development of an insulin drug for oral administration . Orally ingested insulin not only avoids the aforementioned side effects of subcutaneous administration, but also has the advantage of reaching the liver at high concentration via the portal vein before reaching systemic circulation, which better mimics the physiology of endogenous secretion by the pancreas and provides a better glucose homeostasis . However, developing oral insulin remains a major challenge because of its susceptibility to proteases in the digestive system of the human body and poor permeability across the intestinal epithelium upon dimerization, which leads to overall low absorption efficiency . Therefore, proteolytic stability and dimerization propensity are two of the most important controlling factors when developing oral insulin drugs. During past years, a wide array of strategies, including chemical modifications , nano-particulate carrier systems , and utilization of protease inhibitors , have been shown to have varying degrees of success in improving these two insulin properties.