The rising global incidence of atherosclerosis (AS) highlights the inadequacies in our understanding of the pathophysiology and treatment of the disease. Increasing evidence outlines the importance of the intestinal microbiome in AS, wherein gut-derived uremic toxins (GDUTs) may be of concern. Plasma levels of the GDUTs trimethylamine n-oxide (TMAO), p -cresyl sulfate, and indoxyl sulfate are associated with accelerated renal function decline and increased cardiovascular risk. Thus, reducing the amount of GDUTs in circulation is expected to benefit patients with AS. Because some beneficial bacteria can clear GDUTs in vitro and in vivo , orally administered probiotics targeting the intestinal tract represent a promising way to bring about these changes. As such, this perspective reviews the potential use of probiotics to treat AS, particularly in patients with non-traditional risk factors and/or impaired renal function.