This study was aimed to investigate the effects of water extracts of Graptopetalum paraguayense (WGP, 4 g/d) on blood pressure, blood glucose level, and lipid profiles in subjects with metabolic syndrome (MS). Participants with MS (n = 54) were randomly assigned to the placebo (n = 28) and WGP groups (n = 26), and the intervention was administered for 12 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), lipid profiles (total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein (HDL-C)), and antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) were measured. Forty-two subjects completed the study (placebo, n = 19; WGP, n = 23). FG, SBP, and LDL-C levels were significantly lower and HDL-C level and antioxidant enzymes activities (CAT and SOD) were significantly higher after WGP supplementation. Blood pressure, FG, and lipid profiles were significantly correlated with antioxidant enzymes activities after supplementation (P < 0.05). The present study demonstrated a significant reduction in blood pressure, blood glucose, and lipid profiles and an increase in antioxidant enzymes activities in subjects with MS after WGP supplementation. Taken together, the antioxidative capacity of WGP might exert a beneficial effect on MS. This trial is registered with ClinicalTrials.gov NCT01463748.