The high demand for molecular oxygen, the enrichment of polyunsaturated fatty acids in membrane phospholipids, and the relatively low abundance of antioxidant defense enzymes are factors rendering cells in the central nervous system (CNS) particularly vulnerable to oxidative stress. Excess production of reactive oxygen species (ROS) in the brain has been implicated as a common underlying factor for the etiology of a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. While ROS are generated by enzymatic and nonenzymatic reactions in the mitochondria and cytoplasm under normal conditions, excessive production under pathological conditions is associated with activation of Ca²⁺-dependent enzymes including proteases, phospholipases, nucleases, and alterations of signaling pathways which subsequently lead to mitochondrial dysfunction, release of inflammatory factors, and apoptosis. In recent years, there is considerable interest to investigate antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we describe oxidative mechanisms associated with AD, PD, and stroke, and evaluate neuroprotective effects of phenolic compounds, such as resveratrol from grape and red wine, curcumin from turmeric, apocynin from Picrorhiza kurroa, and epi-gallocatechin from green tea. The main goal is to provide a better understanding of the mode of action of these compounds and assess their use as therapeutics to ameliorate age-related neurodegenerative diseases.