Oxidative stress-induced cell damage has been implicated in a variety of neurodegenerative disorders. Morroniside, an iridorid glycoside isolated from Cornus officinalis Sieb. Et Zucc., has shown potent antioxidant properties. The present study investigated the protective actions of morroniside against the cytotoxicity produced by exposure to H2O2 (300–500 μM) in SH-SY5Y cells. Intracellular accumulation of Ca2+, and decreases in mitochondrial membrane potential (MMP) caused by added H2O2 were reduced by morroniside. Incubation of cells with H2O2 caused a marked decrease in superoxide dismutase (SOD) activity; this decrease was significantly inhibited by morroniside. In addition, the percentage of cells undergoing H2O2-induced apoptosis was decreased, dose dependently, in the presence of morroniside. These results suggest that morroniside has protective effects against oxidative stress-induced neurotoxic processes.