The blood-brain barrier (BBB) is a dynamic barrier between the peripheral circulatory system and brain tissue, whose permeability to polypeptide drugs has a direct impact on the effect of drugs on the central nervous system (CNS). With the development of neuroscience and genetic engineering technology, a large number of protein and polypeptide drugs have been applied to the treatment of nervous system diseases. Many protein and polypeptide drugs have biological activities on the CNS, but the BBB prevents these substances from entering the CNS and exerting therapeutic effects. The mechanisms of transport of peptides and ways of promoting the penetration of the BBB by polypeptide drugs are summarized in this article and proteins or peptides known to penetrate the BBB are introduced. It is hoped that this paper will provide some direction for the development of CNS drugs.