The gut microbiota produces a wide range of metabolites that, through their actions on T cells, B cells, and innate immune cells, reshape immune cell differentiation and function to regulate intestinal immunity. Moreover, microbiota-derived metabolites are closely linked to the nervous system and systemic metabolism and are also associated with the development and progression of cancer and various chronic diseases. Recently, several microbiota-derived tryptophan(Trp) metabolites have attracted attention because of their strong association with antitumor immunity within the tumor microenvironment(TME). In this review, we first summarize the molecular and cellular mechanisms by which gut microbiota-derived Trp metabolites regulate intestinal immune homeostasis and then examine the latest evidence on how these metabolites influence diverse diseases via systemic circulation. We further describe how microbiota-derived Trp metabolites interact with diverse immune cell subsets in the TME to shape antitumor immunity. Finally, based on these immunoregulatory properties, we outline future therapeutic strategies and research directions for exploiting Trp metabolites in the context of antitumor immunity.