Abstract: Subcutaneous insulin injection is mainly used to treat diabetes, but it has limitations, such as hyperinsulinemia, adipose tissue atrophy and hypoglycemia. As a simple way of administration, oral insulin can reduce side effects and improve patients’ compliance. However, protein drugs can be inactivated by gastrointestinal enzymes after oral administration. In recent years, with the rapid development of nanotechnology, targeted nano-delivery systems have been widely used in the study of oral insulin. Compared with unmodified nanocarriers, targeted nano delivery system has obvious advantages. Insulin can not only be loaded by it, but also smoothly pass through the gastrointestinal barrier and be successfully transported to the site of action. At the same time, the structural stability of insulin can also be protected, so as to maintain its biological activity and finally achieve mild hypoglycemic effect. Therefore, targeted oral delivery of insulin is promising to replace the common subcutaneous injection of insulin and provide painless treatment for diabetic patients. The ligand-modified targeting nanocarriers enhance the intestinal absorption and transport of insulin by specifically binding to receptors on the surface of intestinal cells and play a mild hypoglycemic effect. The main characteristics, targeting mechanism and main factors affecting the targeting effect of targeting nanocarriers are discussed. The main factors include the size, shape and ligand density of nanoparticles. The design ideas, research methods and oral bioavailability of nano-carriers modified with different surface ligands are reviewed in detail. These targeting ligands are folic acid (FA), fragment crystallizable (Fc), biotin, polypeptide, transferrin and VB12. The existing problems and future development directions of targeting nanocarriers for oral insulin are also put forward.