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Sesame (Sesamum indicum L.) is a worldwide cultivated oil crop that belongs to the family Pedaliaceae. Sesame seeds possess high nutritional value, enriching fats, proteins, carbohydrates, and vitamins. Various phytochemical constituents are found in sesame seeds and/or oil, such as phenolic acids, flavonoids, phytosterols, tocopherols, phospholipids, and unique class of lignans such as sesamin and sesamolin, showing specific health potential to the human body (antioxidant, antimutagenic, estrogenic, anti-inflammatory, antimicrobial and hypolipidemic). Bioavailability is composed of two components: bioactivity and bioaccessibility. However, because phytochemicals are treated by the body as xenobiotics, their bioavailability is poor, and their presence in the body is temporary. Although specific methods for determining phytochemical bioavailability in sesame are being established using both in vitro and in vivo approaches, the results are still inconclusive. Several factors will impact bioavailability in the human body, including molecular structure, transport mechanisms, and food-drug interactions. To improve the bioavailability of phytochemicals in sesame and thereby enhance the bioactivities, specific methods such as the application of sesamol solid lipid nanoparticles, the application of colloidal systems, and changing the solubility of phytosterols will be discussed. [ABSTRACT FROM AUTHOR]