Stoke is a global threat, leading to 50 % of deaths worldwide and it causes permanent disability to about 5 million individuals globally each year. In this study, we assessed the potency of tomentosin to inhibit the neuroinflammation in in vivo and in vitro models. The Sprague Dawley rats were pretreated with 25 mg/kg bodyweight (b.wt) and 50 mg/kg b.wt of tomentosin for seven days followed by induction of cerebral ischemic reperfusion. The brain edema and cerebral infractions were analyzed. The levels of antioxidants and the interleukins were measured by standard methods. The NLRP3 signaling proteins expression was evaluated using qPCR analysis. In vitro studies were performed in SH-SY5Y-cells pretreated with tomentosin and subjected to OGD-R treatment. Our results depicts tomentosin scavenges the free radicals, enhances antioxidant system, inhibits the NLRP3 signaling. In vitro results substantiates with in vivo results. To conclude, our in vivo and in vitro results confirm tomentosin may be potent alternative for existing antistroke drugs.