Ischaemic stroke is a typical cerebrovascular illness with high morbidity and mortality worldwide. Nevertheless, strategies for the prevention and treatment of cerebral ischaemia-reperfusion injury (CIRI) are limited. Gallic acid (GA) is a plant polyphenol that has been used against CIRI. However, the pharmacokinetic properties of GA, such as its low absorption, poor bioavailability and quick elimination, have had negative effects on its scientific application. To strengthen its effectiveness, a delivery system of GA-loaded o-carboxymethyl chitosan nanoparticles (GA-NPs) was synthesized in our study. GA nanoparticles were prepared, and their effects were evaluated. We measured the in vitro and in vivo effects of the GA-NPs in the oxygen glucose deprivation (OGD) model and the middle cerebral artery occlusion (MCAO) model. We established an OGD model to study the neuroprotective effects of GA-NPs. We established an in vivo MCAO model to measure neurological deficit scores with the Zea Longa neurological deficit scale, infarct size by TTC staining, apoptosis by TUNEL staining, and antioxidant and anti-inflammatory indicators by ELISA. The results showed that GA-NPs improved neurological defects, reduced infarct size, decreased TUNEL-positive cells, and alleviated pro-inflammatory and oxidative stress responses. In conclusion, GA-NPs may be used as an efficacious delivery vehicle for GA in the treatment of CIRI.