Carbapenem-resistant Enterobacteriaceae (CRE) represent a critical antimicrobial resistance threat due to their resistance to last-resort antibiotics and high transmission potential. While conventional strategies-such as infection control, antimicrobial stewardship, and novel antibiotic development-remain essential, growing attention has shifted toward the gut microbiome, which plays a central role in mediating colonization resistance against CRE. Disruption of the intestinal microbiota-primarily driven by antibiotic exposure and further exacerbated by non-antibiotic drugs such as proton pump inhibitors-reduces microbial diversity and impairs functional integrity, facilitating CRE acquisition, prolonged carriage, and horizontal transmission. In response, microbiome-based strategies-including microbiome disruption indices (MDIs), fecal microbiota transplantation (FMT), and rationally designed symbiotic microbial consortia-are being explored as novel approaches for CRE prevention and decolonization. Mechanistic studies have shown that colonization resistance is mediated by both direct mechanisms (, nutrient competition, short-chain fatty acid production) and indirect mechanisms (, immune modulation via IL-36 signaling). Advances in metagenomics, metabolomics, and culturomics have enabled high-resolution profiling of gut microbial communities and their functional roles. Emerging preclinical and clinical evidence supports the potential of microbiome-informed interventions to predict infection risk, enhance antimicrobial stewardship, and guide the development of next-generation probiotics targeting CRE. Longitudinal studies continue to evaluate the efficacy of FMT and synthetic microbial consortia in eradicating intestinal CRE colonization. Collectively, these insights underscore the promise of gut microbiome science as a complementary and innovative strategy for CRE control in the post-antibiotic era.