Steroids and non-steroidal anti-inflammatory drugs (NSAIDs) are the main choices for controlling inflammation. However, their adverse effects limit their clinical use. Sesame (Sesamum indicum L.) is one of the oldest cultivated plants in the world. Its extracts, such as sesame oil, have been widely used since ancient times. Recently, sesame oil and its lignan sesamol have been proved to be potent anti-inflammatory agents. They have an excellent protective effect against endotoxin-associated inflammatory damage because they inhibit the release of inflammatory mediators. Sesamol also inhibits endotoxins from binding to its receptor; this reduces inflammatory transcription factor NF-?B activation. In summary, sesame oil or sesamol may be beneficial for reducing the inflammatory response in inflammation-associated diseases.