Shukla M.Boonmag S.Boontem P.Govitrapong P.Mahidol University2026-03-082026-03-082026-01-01Biocell Vol.50 No.1 (2026)03279545https://repository.li.mahidol.ac.th/handle/123456789/115611Ischemic stroke is one of the major causes of long-term disability and mortality worldwide. It results from an interruption in the cerebral blood flow, triggering a cascade of detrimental events like oxidative stress, mitochondrial dysfunction, neuroinflammation, excitotoxicity, and apoptosis, causing neuronal injury and cellular death. Melatonin, a pleiotropic indoleamine produced by the pineal gland, has multifaceted neuroprotective effects on stroke pathophysiology. Interestingly, the serum melatonin levels are associated with peroxidation and antioxidant status, along with mortality score in patients with severe middle cerebral artery infarction. Melatonin exhibits strong antioxidant, anti-inflammatory, and anti-apoptotic properties and preserves mitochondrial function and homeostasis. Several preclinical studies have shown that melatonin administration conserves blood-brain barrier integrity, reduces infarct size, and edema. These mechanisms contribute to minimizing tissue damage and improving the neurological outcomes following ischemic events. Therefore, the present review evaluates evidence from experimental studies furthered with limited clinical investigations and explores the mechanistic pathways of melatonin functions to establish its therapeutic potential in stroke management.Biochemistry, Genetics and Molecular BiologyReviewSCOPUS10.32604/biocell.2025.0725572-s2.0-10503151172316675746