The aim of this study is to investigate the effects and mechanism of action of sodium butyrate (SB) on brain injury repair in neonatal rats. 126 neonatal SD rats were randomly allocated to 7 groups, and necrotizing enterocolitis (NEC) and hypoxic-ischemic brain injury (HIBI) rat models were established. Hematoxylin and eosin staining showed that SB intervention alleviated intestinal and brain injuries in the HIBI + SB, NEC + SB, and NEC + HIBI + SB groups. Compared to the NEC and NEC + HIBI groups, the NEC + SB and NEC + HIBI + SB groups had significantly higher interleukin (IL)-10 and lower IL-17 levels ( < 0.05). Immunohistochemistry revealed increased Bcl-2 expression and decreased Bax expression in the NEC + SB and NEC + HIBI + SB groups compared to the NEC and NEC + HIBI groups in intestinal and brain tissues ( < 0.05). Compared to the control group (CG), gut microbiota diversity decreased in the HIBI, NEC, and NEC + HIBI groups, and increased significantly in the HIBI + SB, NEC + SB, and NEC + HIBI + SB groups. SB may alleviate brain injury by modulating gut microbiota, affecting IL-10 and IL-17 levels, and regulating Bcl-2 and Bax expression in intestinal and brain tissues.