Sesame is principally used to generate oil, which is produced by chemical refining or pressing. Sesame meal, as a main byproduct of sesame oil extraction, is usually discarded, causing resource waste and economic loss. Sesame meal is rich in sesame protein and three types of sesame lignans (sesamin, sesamolin, and sesamol). Sesame protein extracted via a physical method and an enzymic method has balanced amino acid composition and is an important protein source, and thus it is often added to animal feed and used as a human dietary supplement. Extracted sesame lignan exhibits multiple biological activities such as antihypertensive, anticancer, and cholesterol-lowering activities, and therefore it is used to improve the oxidative stability of oils. This review summarizes the extraction methods, functional activities, and comprehensive utilization of four active substances (sesame protein, sesamin, sesamolin, and sesamol) in sesame meal with the aim to provide theoretical guidance for the maximum utilization of sesame meal.