Phytochemicals and plant extracts, present in fruit, vegetables, plants, herbs, and beverages, have been shown to have antioxidant potential that may modulate the etiology of certain chronic diseases. The objective of the present study was to determine the concentration of compound that inhibited cell growth by 50% (IC50) of a range of phytochemicals and plant extracts and to investigate their antioxidant and genoprotective effects under conditions of oxidative stress in U937 cells. Two phytochemicals-resveratrol and citroflavan-3-ol-and four plant extracts-grapeseed polyphenols, olive leaf extract, bearberry, and Echinacea purpurea-were examined. Viability was assessed by the fluorescein diacetate/ethidium bromide assay. The IC50 was calculated. To examine their antioxidant and genoprotective effects, U937 cells were pretreated with the test compounds at levels below the IC50 and then exposed to oxidants: 0.5 mu M etoposide or 100 mu M hydrogen peroxide (H2O2) or 400 mu M tert-butylhydroperoxide (tBOOH). Cellular reduced glutathione levels were measured as an indicator of oxidative stress. DNA damage was assessed by the alkaline single-cell gel electrophoresis assay or comet assay. Resveratrol demonstrated the highest IC50 value of 13.7 mu g/mL, with Echinacea the lowest at 9,400 mu g/mL. Etoposide-induced oxidative stress was strongly reduced by olive leaf extract and bearberry. Grapeseed polyphenols and bearberry strongly protected against H2O2- and tBOOH-induced DNA damage. In conclusion, these results provide evidence that non-nutrient dietary constituents may act as significant bioactive compounds and that plant extracts, such as bearberry, grapeseed polyphenols, and olive leaf extract, strongly protect against oxidative stress.