Colorectal cancer (CRC) is among the most prevalent cancers worldwide, with the microbiome playing a significant role in cancer progression and treatment. Numerous studies have demonstrated a strong correlation between microbial metabolites and the development of CRC. Current CRC treatments, such as chemotherapy, radiotherapy, and immunotherapy, while effective, are constrained by issues of toxicity and resistance. The gut microbiota interacts with anticancer drugs through pharmacokinetic and pharmacodynamic mechanisms, significantly impacting treatment outcomes. Additionally, gut microbiota can serve as valuable biomarkers for CRC diagnosis and therapy. This chapter delves into targeted CRC therapies utilizing probiotics, prebiotics, fecal microbiota transplantation (FMT), and bacteriophages. These therapies offer a novel approach to CRC treatment but present several challenges, including individual variability, lack of standardized protocols, potential adverse effects, safety concerns, and regulatory and ethical issues. The future of CRC treatment will likely focus on the modulation of the gut microbiome, which can be readily altered to enhance treatment efficacy. This strategy is anticipated to be pivotal in next-generation personalized medicine, improving CRC treatment outcomes through precise microbiome modulation.