Oxidative stress plays a critical role in cerebral ischemia-reperfusion injury. We previously developed a powerful antioxidant, HL-008, and this study aimed to investigate the neuroprotective function of HL-008. The in vitro and in vivo efficacy of HL-008 was evaluated using a PC-12 cell oxidative stress model induced by hydrogen peroxide and a rat model of middle cerebral artery occlusion, respectively. The MTT assay was used to analyze cell viability. TTC staining, HE staining, immunofluorescence, western blot, and proteomics were used to evaluate the infarction volume, brain tissue morphology, apoptosis, inflammation, and related pathways. Indicators related to oxidative levels were mainly detected using commercial kits. HL-008 significantly reduced the cerebral infarction area induced by ischemia-reperfusion, improved the neurological score, alleviated oxidative stress and inflammation in the brain tissue, reduced glial cell activation, inhibited brain tissue apoptosis by influencing multiple signaling pathways, and had a neuroprotective effect. If HL-008 is successfully developed, it can significantly improve the quality of life of stroke patients.