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Background. Endothelial dysfunction is the hallmark of vascular complications in cardiovascular disease with type 2 diabetes as the comorbid. Garcinia mangostana L., or mangosteen, has been known as the queen of fruits from Southeast Asia that owns anti-inflammatory and anti-oxidant properties for years. This study was aimed to evaluate the role of G. mangostana extract as a potent protective vascular endothelium in patients with type 2 diabetes and high-risk Framingham score. Methods. This is a prospective, randomized, single blind, placebo-controlled trial in subjects with type 2 DM and high-risk Framingham score. Subjects were randomly divided into two groups: one group of G. mangostana extract, administered 2,175 mg/day in divided dosage for 90 days, and control group receiving placebo. The primary endpoint was the changes in endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) levels; whereas nitric oxide (NO), IL-1, IL-6, TNF-, fasting blood glucose and HbA1c were also evaluated. Study had been approved by local ethics committee. Statistical analysis was done and p<0.05 considered significant. Results. From 90 subjects with high-risk Framingham score, there were 49 (54.4%) subjects with type 2 diabetes, which randomly divided into two groups. The treatment group (n=23) received G. mangostana extract and control group (n=26) received placebo. Statistical analysis showed that increase of EPC and decrease of CEC levels were significant in treatment group, compared to control (p=0.000 and p=0.002, respectively). The levels of NO increased significantly (p=0.027) and levels of IL-1, IL-6, TNF- decreased significantly in comparison to placebo (p=0.003, p=0.002, p=0.000, respectively). Analysis also showed that HbA1c decreased significantly (p=0.002) compared to placebo; however, it was insignificant for fasting blood glucose reduction (p=0.336). Conclusion. Garcinia mangostana L. extract, as an adjuvant therapy, plays a role in improving endothelial dysfunction by significant increase in EPCs and decrease in CECs, in patients with type 2 diabetes and high-risk Framingham score.