BACKGROUND: Neonatal brain injury due to bilirubin toxicity presents critical need for effective healing treatments. Docosahexaenoic acid (DHA), having neuroprotective properties, offers potential therapeutic benefits in promoting brain repair and recovery. OBJECTIVES: This study focused on evaluating the healing capabilities of DHA in neonatal brains damaged by bilirubin-induced injury, with particular attention to its role in enhancing brain tissue repair mechanisms. METHODS: Employing the bilirubin encephalopathy model in neonatal Sprague-Dawley rats and neuronal cell cultures, we investigated the therapeutic impact of DHA. RESULTS: The study measured improvements in brain tissue integrity, assessed bilirubin levels, analyzed gene and protein expressions pertinent to the brain's recovery process. DHA administration resulted in significant repair in neonatal brains, evidenced by reduction in bilirubin levels and restoration of normal brain tissue architecture. CONCLUSION: Molecular analysis indicated the distinct modulation of the CTBP1/miR-155-5p/KDM5A pathway, critical for cellular repair processes and marked decrease in markers of cellular damage and stress.