<p>T cells, a cornerstone of the adaptive immune system, have pivotal roles at the host–microorganism interface. The gut microbiome profoundly influences T cell biology by producing a diverse repertoire of small molecules that are sensed by host cells. These microbial metabolites regulate all aspects of the T cell lifecycle, from cell development to differentiation and activation to exhaustion. Recent studies have uncovered microbially derived molecules, including short-chain fatty acids, secondary bile acids and tryptophan metabolites, as potent regulators of T cell function. However, the full scope of microbial metabolite–T cell interactions remains largely unexplored. This Review presents a mechanistic framework linking gut microbial metabolites to discrete stages of T cell fate and function. Expanding our understanding of these intricate host–microbiome interactions will reveal new aspects of immune regulation and inspire microbiome-guided therapeutic strategies for infections, autoimmune diseases and cancer immunotherapy.</p>