Neonatal hypoxic ischemic brain injury (HIBD) is the main cause of neonatal mortality and neurological dysfunction in infants. Until now, the hypothermia therapy is the only effective treatment of neonatal HIBD. In recent years, with the development of new technologies, peptide drugs have attracted extensive attention due to their advantages including high selectivity, high efficiency, excellent tolerability, simple preparation process and low cost. Using neonatal HIBD models, it was revealed that many kinds of peptide drugs could enter neurocytes directly or through combining with cell penetrating peptides and play roles of brain protection through inhibiting apoptosis, reducing excitotoxicity, improving mitochondrial permeability and so on. Peptide drugs may become new therapeutic approaches of neonatal HIBD. This article reviews the latest research advances in these peptide drugs and provides a new idea for the treatment of neonatal HIBD.