In parallel with an increased focus on climate changes and carbon footprint, the interest in plant-based diets and its potential health effects have increased over the past decade. The objective of this systematic review and meta-analysis was to examine the effect of vegan diets (≥12 weeks) on cardiometabolic risk factors in people with overweight or type 2 diabetes. We identified 11 trials (796 participants). In comparison with control diets, vegan diets reduced body weight (−4.1 kg, 95% confidence interval (CI) −5.9 to −2.4, p < 0.001), body mass index (BMI) (−1.38 kg/m², 95% CI −1.96 to −0.80, p < 0.001), glycated hemoglobin (HbA_1c) (−0.18% points, 95% CI −0.29 to −0.07, p = 0.002), total cholesterol (−0.30 mmol/L, 95% CI −0.52 to −0.08, p = 0.007), and low-density lipoprotein cholesterol (−0.24 mmol/L, 95% CI −0.40 to −0.07, p = 0.005). We identified no effect on blood pressure, high-density lipoprotein cholesterol, and triglycerides. We found that adhering to vegan diets for at least 12 weeks may be effective in individuals with overweight or type 2 diabetes to induce a meaningful decrease in body weight and improve glycemia. Some of this effect may be contributed to differences in the macronutrient composition and energy intake in the vegan versus control diets. Therefore, more research is needed regarding vegan diets and cardiometabolic health.