Cerebral ischemia/reperfusion injury has emerged as an intricate mechanism. However, identification of wide-ranging mechanisms which mechanistically regulate reperfusion injuries have significantly improved our understanding. Recent advancements in our knowledge about the molecular consequences of ischemia and reperfusion might be advantageous in the development of innovative therapeutic strategies for the treatment of patients with ischemia and reperfusionassociated organ dysfunction and tissue inflammation. Some of the extensively studied mechanisms of reperfusion injury consist of oxidative stress, mitochondrial mechanisms, infiltration of leukocytes, activation/aggregation of the platelets, complement activation, and disruption of the blood-brain-barrier (BBB), which eventually results in the brain oedema or haemorrhagic transformations. In this review, we have attempted to provide a review of the protein networks involved in the regulation of cerebral ischemia reperfusion injury and how different natural products have shown potential in the amelioration of reperfusion induced injuries.