BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor. Immune checkpoint inhibitors (ICIs), particularly those targeting programmed cell death protein 1(PD-1) and programmed cell death ligand 1(PD-L1), have shown promising potential in the treatment of CRC. Specific gut microbiota can modulate the efficacy of ICIs through immune or metabolic pathways. This review summarizes recent advances in the combined application of gut microbiota and PD-1/PD-L1 inhibitors in the treatment of CRC, aiming to provide insights for expanding clinical treatment options for CRC. MATERIALS AND METHODS: We employed a systematic search strategy to screen relevant literature from databases such as PubMed, EMBASE, Medline, Cochrane Library, and Clinical Trial registries, with the search period covering from the inception of each database to October 2024. This study includes animal models and human trial subjects. Data extraction and literature screening were strictly carried out by two independent researchers. RESULTS: A total of 8 animal studies and 5 clinical trials were included to evaluate the effects of gut microbiota combined with PD-1/PD-L1 inhibitors in CRC. Tumor types included Microsatellite Stability(MSS), Microsatellite Instability-Low(MSI-L), and MSI-H CRC. Main outcomes were tumor volume, weight, and incidence; one study reported survival. Study durations ranged from 20 days to 26 weeks. Two studies used human fecal microbiota transplantation(FMT), and six applied experimental microbial interventions. The 5 clinical trials used ORR as the primary endpoint.Some also reported DCR, PFS, and OS. Two studies targeted Microsatellite Instability-High(MSI-H)/Deficient Mismatch Repair(dMMR), two MSS/Proficient Mismatch Repair(pMMR), and one lacked molecular subtype specification. All trials used full microbiota transplantation; one has released preliminary data. CONCLUSION: The treatment regimen combining gut microbiota with PD-1/PD-L1 inhibitors has shown promising therapeutic prospects in both animal studies and clinical research, although most clinical trials are data remain limited. Future studies should focus on: (1) gene-edited probiotic strains with targeted modifications; (2) the synergistic effects of multiple probiotics; and (3) conducting high-quality, multicenter clinical trials.