There is increasing evidence supporting the relationship between imbalance of gut microbiota and development of chronic kidney and cardiovascular diseases. This study aimed to investigate the effect of synbiotic supplementation on plasma levels of advanced glycation end products (AGEs) and cardiovascular risk factors in hemodialysis (HD) patients. In this randomized, double-blind, placebo-controlled clinical trial, 36 HD patients were randomly allocated into two groups to receive two synbiotic supplements ( = 19) or placebo ( = 17) daily for 12 weeks. Levels of AGEs, fibrinogen, hemoglobin A1c (HbA1c), and other measures were assessed at the beginning and end of the study. The data were analyzed using independent t-tests, paired t-tests, and analysis of covariance (ANCOVA). At the end of the study, the plasma levels of AGEs increased significantly in both the synbiotic ( < .001) and control ( = .001) groups, but the difference between the groups was not significant ( = .272). Plasma levels of fibrinogen decreased specifically within the synbiotic group ( = .007), and a statistically significant disparity between the groups persisted at the study's conclusion ( = .016). The mean levels of blood urea nitrogen (BUN) decreased ( < .05) in both groups, but there was no difference between the two groups at the end of the study ( = .116). No significant differences were observed in other measured biomarkers. Synbiotic supplementation improved plasma fibrinogen and BUN levels in HD patients, but did not significantly improve AGEs and HbA1c. Further investigations are needed to investigate the effect of probiotics on AGEs in HD patients at different stages of kidney disease.