Lignans are large group of polyphenols that are formed by the coupling of two coniferyl alcohol residues. Based on their origin, lignans are broadly grouped into plant lignans such as isolariciresinol, secoisolariciresinol diglucoside, lariciresinol, and matairesinol; and mammalian lignans such as enterodiol and enterolactone. Based on the oxidation level of the lignan skeleton, they are also categorized into numerous groups such as dibenzylfuran, dibenzylbutyrolactol, dihydroxybenzylbutane, arylnaphtalene and aryltetraline lactone derivatives. Depending on structural type and concentration, numerous dietary lignans have been shown to possess biological activities including protective effect against diseases such as hormone-dependent tumors and cardiovascular diseases. Also, they display antioxidant properties in tissues and organs including the liver and the brain, lignans are found in most fiber-rich seeds such as sesame and pumpkin, and grains including barley, wheat, oats and rye. This paper focus on the metabolism in humans, and recent studies on the antioxidant and possible prooxidant effects of lignans at three levels: in vitro, in vivo in animals and clinical studies. Key Findings and Conclusions: Most of the studies investigating the antioxidant effect of lignans were in vitro and animal models and only five clinical trials were found; one evaluating the effect of enterolactone on low-density lipoprotein (LDL) peroxidation and four investigating the effects of plant lignans including flaxseed lignan components, secoisolariciresinol and sesamin on lipid peroxidation. So, lignans seem to be a valuable source for identifying new molecules for preventing various diseases especially cardiovascular disorders. Since most of studies are preclinical, however, further clinical trials are required to achieve more conclusive results.