Tryptophan (Trp) is an essential amino acid which is unable to be synthesized in the body. Main sources of Trp are uptake of foods such as oats and bananas. In this review, we describe the status of current dietary consumption, metabolic pathways and nutritional characteristics of Trp, as well as its ingestion and downstream metabolites for maintaining body health and safety. This review also summarizes the recent advances in Trp metabolism, particularly the 5-HT, KYN, and AhR activation pathways, revealing that its endogenous host metabolites are not only differentially affected in the body but also are closely linked to health. More attention should be paid to targeting its specific metabolic pathways and utilizing food molecules and probiotics for manipulating Trp metabolism. However, the complexity of microbiota−host interactions requires further exploration to precisely refine targets for innovating the gut microbiota-targeted diagnostic approaches and informing subsequent studies and targeted treatments of diseases.