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Squalene is a polyunsaturated triterpenoid compound present in various organisms. Squalene has multiple biological activities, which makes it a potential new functional food ingredient for nutrition enhancement or disease prevention. However, low extraction efficiency, high cost, and environmental issues greatly limit the practical application of squalene. This review discusses the latest findings on the biological activities, natural and genetically modified organism (GMO) sources, trends of extraction technologies, and delivery systems of squalene, providing innovative prospects for the large-scale production and application of squalene. Key findings and conclusions: Squalene has various biological activities, such as immunity enhancement, skin senility resistance, and hypolipidemic, antioxidant, antitumor, antibacterial, and detoxification effects. Thus, squalene can be widely applied in the food and pharmaceutical industries. Natural and GMO sources provide the foundation for large-scale squalene production. Innovative, green, sustainable extraction technologies are emerging as substitutes for traditional technologies. In addition, delivery systems can be used to maintain oxidation stability and efficacy of squalene in food applications. • Biological activities of squalene are presented. • Natural and GMO sources of squalene are summarized. • The advantages and limitations of squalene extraction technologies are discussed. • Delivery systems are beneficial for the application of squalene in food and drug. [ABSTRACT FROM AUTHOR]