Due to the crucial role of oxidative stress in the stress-induced memory deficit, the benefit of substance possessing antioxidant effect is focused. Since no data are available, we aimed to determine the effect of Nelumbo nucifera flowers extract on spatial memory and hippocampal damage in stressed rats. Male Wistar rats, weighing 250–350 g, were orally given N. nucifera extract at doses of 10, 10, and 200 mg·kg−1 45 minutes before the exposure to 12-hour restraint stress. The spatial memory and serum corticosterone were assessed at 7 and 14 days of study period. At the end of study, acetylcholinesterase (AChE), monoamine oxidase type A and monoamine oxidase type B (MAO-A and MAO-B), oxidative stress status, neuron density, and Ki67 expression in hippocampus were also assessed. The results showed that N. nucifera extract decreased memory deficit and brain damage, serum corticosterone, oxidative stress status, AChE, and MAO-A and MAO-B activities but increased neuron density and Ki67 expression in hippocampus. These suggested that the improved oxidative stress status, adult neurogenesis, and cholinergic and monoaminergic functions might be responsible for the protective effect against stress-related brain damage and dysfunction of the extract. Therefore, N. nucifera extract is the potential neuroprotective and memory enhancing agent. However, further researches are still required.