Humans with the metabolic syndrome and type 2 diabetes have an altered gut microbiome. Emerging evidence indicates that it is not only the microorganisms and their structural components, but also their metabolites that influences the host and contributes to the development of the metabolic syndrome and type 2 diabetes. Here, we discuss some of the mechanisms underlying how microbial metabolites are recognised by the host or are further processed endogenously in the context of type 2 diabetes. We discuss the possibility that gut-derived microbial metabolites fuel the development of the metabolic syndrome and type 2 diabetes. Graphical abstract.