The natural active components derived from plants have attracted widespread attention due to their abundant species and source advantages. With the continuous deepening of research, studies have shown that many natural active components have broad-spectrum biological activities, such as antioxidant, antihypertensive, hypoglycemic, anti-inflammatory, antibacterial, anticancer, and enzyme-inhibiting activity properties, which are valuable sources of research and development in functional food factors and novel drugs. Systematical studies on the structure of components, physiological activities, the structure-activity relationship, and mechanisms of action for active components using modern scientific methods and experimental means are hot research topics. In addition, the exploration of the combined effect and mechanism of various natural bioactive substances will provide a theoretical basis for the further processing and comprehensive development of resources at multiple levels and from various points of view. This Special Issue of Foods, entitled "Structure Identification and Functional Mechanism of Natural Active Components", provides a forum for researchers to communicate some of their latest findings in this field.