Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills. In the brains of AD patients, signs of neuronal degeneration are accompanied by markers of microglial activation and inflammation as well as oxidant damage. This study tested the hypothesis that fucoxanthin, which is known to exert a variety of pharmacological properties, would ameliorate oxidative stress and inflammation in amyloid-β42 (Aβ42)-induced BV2 microglia cells. It was found that fucoxanthin treatment attenuated pro-inflammatory secretion in BV2 cells as determined by ELISA analysis. Suppressive effects of fucoxanthin on the phosphorylation mitogen-activated protein kinase (MAPK) pathway were confirmed. Moreover, fucoxanthin was able to inhibit free radical-induced DNA oxidation in BV2 cells. This effect was associated with a significant reduction of intracellular reactive oxygen species (ROS) formation and recovery of antioxidative enzymes. The findings in this study suggest that fucoxanthin may serve as a negative feedback regulator of inflammation and oxidative stress in BV2 cells and thereby may protect neuronal cells from neurotoxic mediators released by microglia.