Abstract: Diabetes mellitus (DM), a common chronic disease, has seriously threatened human health and quality of life. Compared with subcutaneous injection, oral administration of hypoglycemic proteins and peptides (PPs) is a more ideal treatment option for DM. However, there exist several biological barriers that limit the oral absorption efficiency of drugs. Recently, based on the rapid development of materials and technologies in drug formulation, a variety of oral drug carriers that are expected to solve the problems have been developed. This article summarizes the common drug delivery barriers facing oral drug carriers in vivo and highlights the special barriers limiting oral delivery of hypoglycemic PPs. Additionally, the article further reviews the research status and progress of clinical application in related fields with a prospect of their future development, aiming to provide new insights for the rational design of oral delivery carriers for hypoglycemic PPs.