Sesame (Sesamum indicum L.) is one of the most important oilseed crops, having seeds and its edible oil that are highly valued as a traditional food. Many studies have examined the health value of sesame seeds and oil. Among the bioactive components in sesame seeds, lignans and tocopherols have been identified as the major antioxidants responsible for the resistant oxidative deterioration of sesame seeds and oil. These same antioxidants have been reported to have protective effects against human disease such as neurodegenerative disease. This review summarizes the chemical properties of lignans including lipid-soluble lignans, lignan glucosides and tocopherols, and their bioactivities such as antioxidativity and neuroprotection. We also review the biosynthesis of lignan in sesame seeds and transformation of lignans during food processing in sesame oil. Sesame seeds and its antioxidants may be a potent natural agent with both therapeutic applications and use in preventing human illness such as neurodegenerative disease.