Alzheimer's disease (AD), an age-related neurodegenerative disorders, is widely recognized as a serious public health problem. As lifespan increases, greater proportions of our population are affected by AD. AD is characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) observed in the brain tissue. The treatment of AD is currently limited to the symptomatic treatment with two classes of the US FDA approved drugs which are acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonist. These drugs have a limited efficacy and are considered to be effective only in a short period of time. At this point, there is still no approved treatment with a proven disease-modifying effect. This leads to the need for the development of effective compounds that can provide disease-modifying property. Oxidative stress is known to play an important role in AD, and there is strong evidence linking oxidative stress to Aβ. Sesame seed (Sesame indicum) has been known as a natural healthy food in East Asian countries. Many evidences suggested that sesame lignans including sesamin, sesamolin, and sesamol obtained from sesame seed possess antioxidant property. To test whether these sesame lignans exhibit benefit effects in AD, the nematode Caenorhabditis elegans (C. elegans) was utilized. To develop transgenic C. elegans model of AD, human Aβ is expressed intracellularly in the body wall muscle. The expression and subsequent aggregation of Aβ in the muscle lead to paralysis. The mechanism by which Aβ induced toxicity causing worm paralysis is believed to result from oxidative stress. The purpose of this study was to investigate the protective effect of sesame lignans (sesamin, sesamolin, and sesamol) against Aβ toxicity using C. elegans model of AD. Of these three sesame lignans, we found that only sesamin and sesamolin significantly delayed Aβ-induced paralysis. Sesamin and sesamolin delayed the paralysis in this model by 2 h and 1.8 h, respectively. This result suggests that sesamin and sesamolin can reduce Aβ toxicity. The mechanism by which sesamin and sesamolin delaying Aβ-induced paralysis is under investigated.