This review systematically summarizes and discusses the regulatory effects of TPs on gut microbiota, and the microbial biotransformation of TPs into metabolites, as well as the microbial modulation of intestinal 5-HT and the roles of 5-HT and its receptors in intestinal function and homeostasis, with a particular focus on critically evaluating the extent to which current data support the proposed interactions among TPs, gut microbiota, and 5-HT in metabolic disorders. Here, HTR5A is linked to Other metabolic disease.