<p>Nephrolithiasis is associated with an increased risk of cardiovascular disease (CVD) due to dysbiosis in kidney stone formers. This study aimed to investigate the effects of synbiotics on CVD risk factors in overweight or obese calcium oxalate stone formers. In this randomized clinical trial, 44 patients were randomly assigned to either the synbiotic or the placebo group. Participants in the synbiotic group received two synbiotic capsules daily for 12 weeks, while the placebo group received a corresponding placebo. At baseline and at the end of week 12, blood pressure was measured, and 7 mL of blood was collected from each patient. Serum fasting glucose, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and total antioxidant capacity (TAC) were assessed. Serum hs-CRP decreased (<i>P</i> = 0.004; 95% CI 0.313–1.564) and TAC increased (<i>P</i> = 0.001; 95% CI −  146 to − 39) significantly in the synbiotic group compared to the placebo group.<!-- Query ID="Q1" Text="Affiliation [1] has been split into two different affiliations. Please check if action taken is appropriate and amend if necessary." --> No statistically significant difference was observed between the two groups in terms of body weight, BMI, waist circumference, systolic and diastolic blood pressures, serum fasting glucose, and lipid profile at the end of week 12. This study indicates that synbiotic supplementation significantly reduces serum hs-CRP, while increasing serum TAC. Therefore, synbiotics may have beneficial effects on CVD risk factors in patients with kidney stones.</p><p><i>Iranian Registry of Clinical Trials</i> IRCT20120913010826N35 (21/11/2024).</p>