With the advancement of space exploration, space microbiology has become an important research area. Microorganisms show remarkable adaptive plasticity under extreme space environments. Space-derived strains not only pose potential biosafety risks but also serve as valuable biotechnological resources. This review focuses on microbial phenotypic alterations, including colony morphology, biofilm formation, secondary metabolism, pathogenicity, and antibiotic resistance. These changes are mainly driven by genomic instability, horizontal gene transfer, and cellular pathway reprogramming. Here we uniquely integrate phenotypic, mechanistic, and application-level perspectives to provide a unified framework for understanding microbial adaptation in spaceflight environments.