A growing body of evidence suggests that gut microbiota-derived substances play a key role in the control of host body functions including cardiovascular function. Accordingly, various substances converted by gut microbiota can have beneficial or adverse effects on human health. Among them, indoxyl sulfate, which is metabolized in the liver from indole converted from dietary tryptophan by bacterial tryptophanases in the colon, is known as a protein-bound uremic toxin. Trimethylamine N-oxide (TMAO), which is generated via the oxidization of gut microbiota-derived trimethylamine by hepatic flavin monooxygenases, is known as an accelerator of atherosclerosis. Although some reports are investigated the relationship between gut microbiota-derived substances and vascular function, there are few studies focused on the direct effects of indoxyl sulfate or TMAO on vascular responses including endothelium-dependent relaxation. We recently found that these two substances could modulate endothelium-dependent relaxation in rat isolated arteries. In the present symposium, we will focus on the relationship between indoxyl sulfate and TMAO on vascular function. This information will provide a conceptual framework that would allow the development of novel preventive and/or therapeutic approaches against vasculopathies.