A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM) based on data from randomized controlled trials (RCTs). We searched electronic databases including PubMed, Cochrane Library, Embase, and Web of Science to identify clinical trials published up to 31 March 2023. Data was pooled using a random-effects model if significant heterogeneity (I2 > 50%), otherwise use a fixed-effects model. Fifty-six trials that included 3 317 patients were enrolled for analysis. Meta-analysis reported that probiotic/prebiotic/synbiotic supplementation significantly reduced systolic blood pressure (SBP) (weighted mean difference (WMD): ?3.57 mmHg, 95% confidence interval (CI): ?5.36, ?1.78; P = 0.000), diastolic blood pressure (DBP) (WMD: ?2.05 mmHg, 95% CI: ?3.07, ?1.04; P = 0.000), triglycerides (TG) (WMD: ?16.10 mg/dL, 95% CI: ?20.16, ?12.05; P = 0.000), total cholesterol (TC) (WMD: ?14.00 mg/dL, 95% CI: ?20.46, ?7.55; P = 0.000), low-density lipoprotein cholesterol (LDL-C) (WMD: ?7.03 mg/dL, 95% CI: ?9.25, ?4.81; P = 0.000), fasting plasma glucose (FPG) (WMD: ?16.57 mg/dL, 95% CI: ?20.39, ?12.74; P = 0.000), hemoglobin A1c (HbA1c) (WMD: ?0.44%, 95% CI: ?0.68, ?0.20; P = 0.000), insulin (standardized mean difference (SMD): ?0.37, 95% CI: ?0.53, ?0.21; P = 0.000), homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: ?1.05, 95% CI: ?1.56, ?0.54; P = 0.000), C-reactive protein (CRP) (SMD: ?0.35, 95% CI: ?0.57, ?0.13; P = 0.002), tumor necrosis factor-α (TNF-α) (SMD: ?1.07, 95% CI: ?1.57, ?0.56; P = 0.000), interleukin-6 (IL-6) (SMD: ?0.37, 95% CI: ?0.61, ?0.13; P = 0.003) levels, they also increased the high-density lipoprotein cholesterol (HDL-C) (WMD: 3.70 mg/dL, 95% CI: 1.80, 5.60; P = 0.000) levels in T2DM patients, as compared to the placebo groups. This meta-analysis supports the use of probiotic/prebiotic/synbiotic supplementation as an adjunctive therapy to improve blood pressure, glycemic control parameters, lipid profile and inflammatory markers in patients with T2DM, which are well-known cardiovascular risk factors.