Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3–5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b–4 patients on LPD (0.6–0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the pairedt-test showed a significant decrease in TIS and FIS (allp< 0.05) and a significant increase in FMD, eGFR, and bicarbonate (allp< 0.05). In multivariate regression analysis, an increase in FMD (p< 0.001) and a decrease in FPCS (p= 0.012) and TIS (p< 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.