With the development of perinatal medicine, the survival rate of preterm infants has been increasing year by year, but the incidence of brain injury is still high. Although neurorehabilitation can improve brain injury to a certain extent, neurological dysfunction of varied degrees remains inevitably. Recent studies have shown that sirtuin 3 can regulate microglia in the brain to reduce neuronal damage, and has great potential in protecting premature infants from brain injury. This article reviews the neuroprotective mechanism of sirtuin 3 through microglia on brain injury in premature infants, and to provide a theoretical basis for treatment.