As a common complication of chronic kidney disease(CKD), vascular calcification(VC) significantly increases the incidence of CKD-complicated cardiovascular disease (CVD) and mortality. As chronic kidney disease advances and the glomerular filtration rate(GFT) declines, certain solutes, incapable of efficient filtration and elimination, amass within the body, coalescing into uremic toxins which instigate a spectrum of complications, ultimately intensifying mortality rates. Gut-derived uremic toxins(GUT), products of intestinal flora metabolizing and fermenting intestinal substances, significantly influence the trajectory and prognosis of CKD patients, exerting a pivotal role in the genesis of VC. Manipulating uremic toxin levels by modulating the host gut microbiota emerges as a potential means to prevent and manage VC. This discourse delves into elucidating the precise mechanisms through which various commonplace GUT—encompassing small molecules, macromolecules, and protein-bound toxins—impact the evolution of VC. This impact is predominantly observed through their modulation of the host's inflammatory response, oxidative stress, and signaling pathways. These insights offer a potential avenue for the modulation of uremic toxin levels, positing a novel adjunctive therapeutic approach for managing VC.