It is well established that the brain is particularly susceptible to oxidative damage due to its high consumption of oxygen and that astrocytes are involved in a variety of important activities for the nervous system, including a protective role against damage induced by reactive oxygen species (ROS). The use of antioxidant compounds, such as polyphenol resveratrol found in red wine, to improve endogenous antioxidant defenses has been proposed for neural protection. The aim of this study is to evaluate the putative protective effect of resveratrol against acute H2O2-induced oxidative stress in astrocyte cultures, evaluating ROS production, glutamate uptake activity, glutathione content and S100B secretion. Our results confirm the ability of resveratrol to counteract oxidative damage caused by H2O2, not only by its antioxidant properties, but also through the modulation of important glial functions, particularly improving glutamate uptake activity, increasing glutathione content and stimulating S100B secretion, which all contribute to the functional recovery after brain injury.