Abstract: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and is characterized by a multifactorial pathogenesis involving genetic, epigenetic, environmental, and microbial factors. In recent years, the interaction between the gut microbiota and host metabolism has garnered significant attention for its role in CRC development, with the gut microbiota and microenvironment playing pivotal roles in disease initiation and progression. Tryptophan (Trp), an essential amino acid, is metabolized by host enzymes and microbial pathways, thus yielding metabolites that participate in immune regulation, inflammatory responses, and modulation of the tumor microenvironment. This review has summarized the current knowledge on how gut microbiota-regulated tryptophan metabolic pathways, notably kynurenine, serotonin, and indole derivative pathways, contribute to CRC pathogenesis. It further explores how microbial dysbiosis (e.g., enrichment of procarcinogenic bacteria such as Fusobacterium nucleatum and Bacteroides fragilis) exacerbates CRC progression by perturbing tryptophan metabolism. Finally, this review has outlined emerging microbiota metabolism axis-based strategies for CRC prevention and treatment with the aim of providing insights for mechanistic research and clinical management of CRC.