The gut microbiota is implicated in immune system functions. Regulation of the metabolic processes occurring in immune cells is crucial for the maintenance of homeostasis and immunopathogenesis. Emerging data demonstrate that the gut microbiota is an actor in immunometabolism, notably through the effect of metabolites such as short-chain fatty acids, bile acids, and tryptophan metabolites. In this Perspective, we discuss the impact of the gut microbiota on the intracellular metabolism of the different subtypes of immune cells, including intestinal epithelial cells. Besides the effects on health, we discuss the potential consequences in infection context and inflammatory bowel diseases.