Aqueous extracts of Reseda luteola L. used as a dyeing agent for centuries have antioxidant activities. The neuroprotective effect of aqueous herb extracts were investigated against glutamate-induced reactive oxygen species (ROS) insult using mouse hippocampal HT22 and cortical neural cells. Aqueous extracts and the hexane fraction of R. luteola L. effectively attenuated the cytotoxicity of glutamate (5 mM) in both HT22 and primary neural cells derived from the mouse cortex. The neuroprotective effect was attributable to unidentified components and luteolin, which is known as a biologically active constituent. Aqueous extracts of R. luteola L. deserve further study for identification of active components and development of food colorants with health benefits.