Periventricular leukomalacia (PVL) is a brain injury seen in preterm infants and causes a significant social, cultural, and economic burden by introducing permanent disabilities throughout life. Cognitive and motor impairments observed during the follow-up in cases with PVL limit their ability to participate in society. Colostrum milk, the first milk produced after birth, is a unique biological fluid. It is thought to have functions other than nutrition with its contents like microRNAs, extracellular vesicles, and neurotrophic mediators. Studies show that colostrum can be neuroprotective when administered to premature babies with intraventricular hemorrhage. Despite this, the specific mechanisms by which colostrum exerts its neuroprotective effects remain to be determined. We aim to develop a neuroprotective and neurorestorative treatment method with colostrum-derived exosomes that have the capacity to pass through the blood-brain barrier. In line with this, we demonstrated the transition of exosomes in colostrum to brain tissue by PKH67 staining and evaluated their effects on neuronal brain damage in the PVL rat model. Also, the neurorestorative effects of injected colostrum-derived exosomes on the PVL rats were evaluated by Western, ELISA, qPCR, immunofluorescent staining, and behavioral tests. Our study is the first study investigating the penetration of intranasally administered colostrum-derived exosomes into the brain and their effects. We believe that the results will open a different window regarding the therapeutic potential of colostrum in neonatal brain injury, and this approach will be pioneering in the brain injury models with different etiologies.