Chronic degenerative non-communicable diseases (CDNCDs), in particular chronic kidney disease, induce gut microbiota (GM) dysbiosis, which, in turn, worsens the progression of CDNCDs and patients' quality of life. We analyzed literature studies to discuss the possible positive and beneficial impact of physical activity on GM composition and CV risk in CKD patients. Regular physical activity seems to be able to positively modulate the GM, reducing the systemic inflammation and consequently the production of uremic gut-derived toxins, which are directly correlated with the increase of cardiovascular risk. In particular, the accumulation of indoxyl sulphate (IS) seems to be able to induce vascular calcifications, vascular stiffness and cardiac calcifications, while p-Cresyl sulphate (p-CS) seems to be able to exert a cardiotoxic action through metabolic pathways, capable of inducing oxidative stress. In addition, trimethylamine N-oxide (TMAO) can alter lipid metabolism, inducing the production of foam cells and causing an accelerated atherosclerosis process. In this context, a regular physical activity program seems to represent an adjuvant non-pharmacological approach to the clinical management of CKD patients.