Cerebral ischemia are caused by acute interruption of the brain arterial blood supply, typically by a thrombus or embolus, leading to neuronal insult and the remainder damage are caused by blood vessel rupture, leading to hemorrhage. Acidosis and matrix metalloproteinase activation are the central and prominent metabolic feature of ischemic brain. The combined inhibition of MMPs and ASIC1a channels can offer a new therapeutic approach in cerebral stroke management. Moreover, the combined inhibition of MMPs and ASIC1a with flavonoids remains unknown against neuroprotection in animal models of cerebral ischemia. Flavonoids are believed to act as health-promoting substances and some of them have antioxidant and anti-inflammatory properties. Therefore, the target of the present study was in-silico evaluation of the neuroprotective efficacy of quercetin in rat model of focal cerebral ischemia/reperfusion (I/R) injury and efforts were made to analyze its inhibitory effects on MMPs activation and ASIC1a channels mediated downstream survival/damage mechanisms. Thus on the basis of our in-silico studies we hypothesize that quercetin can be a neuroprotective agent in rat model of focal cerebral ischemia/reperfusion (I/R) injury due to its inhibitory effects on MMPs activation and ASIC1a channels mediated downstream survival/damage mechanisms.