Amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD). Moreover, it has been reported that oxidative stress is involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Recently, docosahexaenoic acid (DHA; C22:6) and eicosapentaenoic acid (EPA; C20:5n-3) have been reported to protect against AD. However, these omega-3 fatty acids are frequently obtained from fish oil and may contain heavy metals. In this study, we utilized Nannochloropsis oceanica to produce omega-3 fatty acid. We observed that when urea levels (nitrogen source) were lowered from 2 to 0.2 g/L in Nannochloropsis oceanica cultures, EPA production increased. Moreover, EPA in Nannochloropsis oceanica effectively promoted antioxidant activity to counter the Abetainduced oxidative stress in Neuro-2A cells. These results indicate that Nannochloropsis oceanica may be potentially used as a therapeutic agent or as a functional food that promotes protection against AD.