The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m². Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P<.0001), BMI (2.2 kg/m²; P<.0001), as well as waist (11.9 cm; P<.0001) and hip circumferences (6.3 cm; P=.0001) were observed in the herbal group compared with placebo. An increase in serum adiponectin concentration was also found in the herbal group versus placebo (P=.0008) at study conclusion along with reductions in fasting blood glucose (12.2%, P=.01), cholesterol (13.8%, P=.002), and triglyceride (41.6%, P<.0001) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups. Our findings suggest that the herbal blend appears to be a well-tolerated and effective ingredient for weight management.