© 2006 by Taylor & Francis Group, LLC. The question of the extent to which food or food supplements can protect us from either age- or disease-induced neuro-oxidative stress is an important research issue today. We showed previously, using proteomics technologies, that specific proteins were changed in abundance in normal adult rat brain following ingestion of grape seed extract (GSE), a popular dietary supplement. Since GSE is enriched in polyphenols with documented antioxidant activity, a current focus in our laboratory is determining whether protein oxidations are directly affected by GSE. In this chapter, we review the information obtained in the previous proteomics study of the actions of GSE in normal rat brain and present initial results from ongoing studies on protein oxidations in rodent brain that may be modulated by GSE. These initial results were obtained from a study in which a transgenic mouse model of dementia, the Tg2576 mouse, was fed GSE, and the protein oxidations in its brain homogenate compared with the protein oxidations in the brains of animals that did not receive a GSE-supplemented diet. Following other investigators, we detected oxidized proteins in our brain samples by derivatizing the oxidized proteins with 2,4-dinitrophenylhydrazine (DNPH), and then carried out Western-blot analysis for the derivatized epitope. Initial proteomics results indicate that when fed a diet supplemented with GSE, the anti-dinitrophenyl (DNP) reactivity in the transgenic mouse brain was quantitatively attenuated. Thus, GSE and possibly other antioxidants may have multiple health benefits, including the inhibition of pathology-relevant brain protein oxidations.