The current study investigated the ability of resveratrol to protect RGC-5 retinal ganglion cells in culture against H₂O₂-induced apoptosis and the underlying mechanism of protection. RGC-5 cells were pre-exposed to resveratrol (5, 10, or 20 μM), followed by 200 μM H₂O₂. Cell viability and apoptosis were detected to assess the cell growth, and expression levels of apoptosis-related and MAPK cascade-associated proteins were determined using western blotting. Levels of reactive oxygen species and mitochondrial membrane potential were also tested, as well as the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GSH). At a concentration-dependent way, resveratrol reversed H₂O₂-induced increases in expressions of cleaved caspase-3 and cleaved caspase-9, production of ROS, loss of mitochondrial membrane potential and the expressions of p-p38, p-ERK, and p-JNK. It also promoted the activities of SOD, CAT, and GSH. Furthermore, the agonists of p38, ERK, and JNK partially weakened the protective effects of resveratrol against H₂O₂-induced apoptosis in RGC-5 cells. Thus, resveratrol can protect retinal ganglion cells against H₂O₂-induced apoptosis by suppressing MAPK cascades. The drug therefore shows potential for preventing glaucoma.