F2-isoprostanes are a biomarker of lipid peroxidation, and their measurement has emerged as a reliable approach to assess oxidative stress. However, dietary intervention studies in humans have provided contrasting results following supplementation with antioxidant-rich foods or supplements. In this paper, we have systematically reviewed the evidence about the effect of supplementation with antioxidant-rich foods and galenic antioxidants on isoprostanes levels in humans. Moreover, the association with nonenzymatic antioxidant capacity (NEAC), a biomarker of endogenous antioxidant status, has also been investigated.MEDLINE database was searched using the terms "(isoprostane * OR isoP OR iso-PGF OR epi-PGF) AND (intervention * OR consumption * OR administration * OR supplementation * )," with limits activated "humans" and "English." Abstracts and full texts were screened, from which were selected human intervention studies reporting isoprostanes measurement in biological fluids. The total of the studies carried out with antioxidant-rich foods and antioxidant galenic supplements was 113, reporting 154 interventions. Results suggest that dietary antioxidants modulate successfully the levels of isoprostanes in less than 45% of the interventions. A correspondence between the effect on isoprostane and NEAC has been evidenced, and this correspondence suggests the importance of measuring different biomarkers to obtain a better outline of the redox events following supplementation.