Galantamine is currently used in the treatment of patients with mild-to-moderate Alzheimer’s disease (AD). Although its action is mostly directed at the regulation of cholinergic transmission, galantamine can also afford neuroprotection against amyloid-beta peptide (Aβ), which is involved in AD pathogenesis. In this study, we used cultured rat cortical neurons treated with two forms of Aβ1–40, fresh and previously aged (enriched in fibrils). First, we confirmed that galantamine prevented neurodegeneration induced by both peptide forms in a concentration-dependent manner. Moreover, we observed that when neurons were co-incubated with fresh Aβ1–40 plus galantamine, the amount of amyloid aggregates was reduced. As oxidative conditions influence Aβ aggregation, we investigated whether galantamine prevents oxidative stress induced by this peptide. The data show that either fresh or aged Aβ1–40 significantly increased the amount of reactive oxygen species and lipoperoxidation, these effects being prevented by galantamine. In Aβ1–40-treated neurons, the depletion of reduced glutathione (GSH) seems to be related to the decrease in glutathione peroxidase and glutathione reductase activities. These alterations in the GSH antioxidant system were prevented by galantamine. Overall, these results constitute the first evidence that galantamine can prevent the neuronal oxidative damage induced by Aβ, providing an in vitro basis for the beneficial actions of galantamine in the AD neurodegenerative process.