Phenolic phytochemicals are thought to promote optimal health, partly via their antioxidant effects in protecting cellular components against free radicals. The aims of this study were to assess the free radical-scavenging activities of several common phenolic phytochemicals, and then, the effects of the most potent phenolic phytochemicals on oxidative damage to DNA in cultured cells. Epigallocatechin gallate (EGCG) scavenged the stable free radical, α,α-diphenyl-β-picrylhydrazyl (DPPH), most effectively, while quercetin was about half as effective. Genistein, daidzein, hesperetin, and naringenin did not scavenge DPPH appreciably. Jurkat T-lymphocytes that were pre-incubated with relatively low concentrations of either EGCG or quercetin were less susceptible to DNA damage induced by either a reactive oxygen species or a reactive nitrogen species, as evaluated by the comet assay. More specifically, control cells had a comet score of only 17±5, indicating minimal DNA damage. Cells challenged with 25 μM hydrogen peroxide (H2O2) or 100 μM 3-morpholinosydnonimine (SIN-1, a peroxynitrite generator) had comet scores of 188±6 and 125±12, respectively, indicating extensive DNA damage. The H2O2-induced DNA damage was inhibited with 10 μM of either EGCG (comet score: 113±23) or quercetin (comet score: 82±7). Similarly, the SIN-1-mediated DNA damage was inhibited with 10 μM of either EGCG (comet score: 79±13) or quercetin (comet score: 72±17). In contrast, noticeable DNA damage was induced in Jurkat T-lymphocytes by incubating with 10-fold higher concentrations (i.e., 100 μM) of either EGCG (comet score: 56±17) or quercetin (comet score: 64±13) by themselves. Collectively, these data suggest that low concentrations of EGCG and quercetin scavenged free radicals, thereby inhibiting oxidative damage to cellular DNA. But, high concentrations of either EGCG or quercetin alone induced cellular DNA damage.