Abstract: Cancer is a major global public health issue, and with the increasing incidence, anticancer drugs have gradually become a crucial therapeutic approach. However, the efficacy and toxicity of anticancer drugs often show significant individual variability. Recent studies have highlighted the pivotal role of the gut microbiota in the metabolism of anticancer drugs, significantly influencing the therapeutic effects and adverse effects of these drugs. This review summarized the research progress on the involvement of gut microbiota in drug metabolism, discussing its impact on drug metabolism through three main mechanisms: direct metabolism, indirect regulation, and bioaccumulation. Additionally, the metabolic pathways of commonly used anticancer drugs, such as irinotecan, capecitabine, and cisplatin, under the influence of gut microbiota, as well as their effects on both therapeutic efficacy and adverse reactions, were analyzed. Furthermore, this paper explored the application of gut microbiota modulation strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, providing theoretical and scientific insights for optimizing anticancer drug efficacy, reducing adverse effects, and overcoming drug resistance.