Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by oxygen deprivation during the perinatal period, occurring in 1–8 per 1000 live births. It can lead to severe neurological conditions such as cerebral palsy, epilepsy, and developmental delays. The primary treatment is therapeutic hypothermia, which reduces mortality and disability but is only partially effective and must be initiated within 6 h after birth. Therefore, cell therapy, which has regenerative properties and extends the treatment window, is expected. Cell therapy using umbilical cord blood cells (UC-BCs) and umbilical cord-derived mesenchymal stromal cells (UC-MSCs) has shown protective effects in clinical trials, but further studies are needed to establish a consensus on their effectiveness. Here, we describe in details experimental methods for treating HIE in mice using bone marrow-derived mesenchymal stromal cells (BM-MSCs). Our aim is that the readers can create an appropriate HIE mice model and effectively provide cell transplantation.