Extremophiles are a group of organisms that thrive under extreme environmental conditions (e.g., high/low temperature, pH, salinity, and pressure) in which most life forms find difficulty to survive. Special living conditions lead to their special genetic background and metabolic pathways, and they can produce special enzymes (extremozymes) and active ingredients (extremolytes). As a special microbial community, extremophiles have great potential in biomedicine, bioenergy, biomaterials and other fields. The study of extremophiles is not only related to the origin and evolution of life, but also significant to the development of biotechnology and other fields. This review summarizes the concept of extreme environment and extremophiles, and the potential application of extremophiles and extremozymes in the medical, biorefinery and other fields. In addition, the adaptation mechanism of extremophiles under various conditions and the application of synthetic biology in extremophiles are also introduced. Furthermore, this review explores the challenges in the development of extremophiles and the comprehensive application potential of extremophiles and extremozymes in space and national defense, which is partly due to their specificity and efficiency, and points out the necessity for accelerating A c c e p t e d