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Background: Hyperglycemia on Diabetes is one of risk factor for cardiovascular disease. High glucose induced increases of Reactive Oxygens Species (ROS) Production. High free radical can induce oxidative stress, and endothelial dysfunction in atherosclerosis. In Previous studies, PsP of Ganoderma lucidum has been proven as an antioxidants, anti endothelial dysfunction and no toxicity in animal model. Aim: This study aims to prove the effect of PsP of Ganoderma lucidum as a potent protective endothelial vascular, and antioxidant in STEMI and STEMI patients with diabetes as a risk factor. Method: This clinical trial study conducted to 50 patients according that diagnosed STEMI, NSTEMI and Diabetes, with pre- and post-test control group design. The parameters are MDA, SOD, CEC, and EPC counts. The patients were given PsP 750 mg/day in 3 divided dose for 90 days. Patients divided into two group randomized, one group were given PsP Ganoderma lucidum, and another group were given placebo. Dependent T-test was performed for normally distributed data and Wilcoxon test was performed for abnormally distributed data with significance level of p≤0.05. Results: MDA level significantly decreased with P=0,03 in PsP group patients, SOD significantly increased with P=0,000 in PsP group patients, EPC count significantly increased with P=0,016 in PsP group patients, CEC count significantly decreased in PsP group patients with P= 0,02. Conclusion: Ganoderma lucidum polysaccharide peptides is a potent protective endothelial vascular, and antioxidant against pathogenesis of atherosclerosis in STEMI and NSTEMI patients with diabetes as a risk factor.