Women with colorectal cancer (CRC) have a better survival outcome compared to men of the same age, indicating a global incidence of sexual dimorphism in CRC rates and survival. However, an ongoing discussion on the clinical implementation of sex-biased precision medicine for CRC. We will explain the potential causes of sexual dimorphism in CRC from the sex-biased gut microbiota and metabolites. First, we edified that males have a shorter survival rate compared to females in both ApcMin/+ and AOM/DSS mouse models of CRC. The sex difference in survival rate disappears after gut microbiome depletion using antibiotics attenuated mice. Then, we found that the significant shift of gut microbiota composition with increased pathogenic bacteria Alistipes inops and Akkermansia muciniphila and depleted probiotic Parabacteroides goldsteinii, Lactobacillus taiwanensis and Lactobacillus fermentum, along with more impaired gut barrier function was exhibited in male mice. In addition, gut metabolites alteration, including elevated LPC, which was confirmed to promote CRC cell proliferation and impair cell junction, was also observed in male mice. Moreover, transfer of stools from male mice to pseudo germ-free mice increased colonic cell proliferation, impaired gut barrier function, and disordered gut microbiome. Similarly, we obtained the same results when fecal samples from male CRC patients were transferred into pseudo germ-free mice. Our results reveal that sex-difference in gut microbiome is one of the potential causes of sexual dimorphism in CRC, providing new insights for precise prevention and treatment of colorectal cancer.