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Background: Obesity is one of the most prevalent metabolic disorders worldwide, and its long-term management remains challenging due to the limited efficacy and adverse effects of current pharmacological treatments. Accordingly, there is growing interest in safe and effective anti-obesity strategies based on natural compounds. This study aimed to evaluate the anti-obesity effects of HT099, an extract derived from Prunus persica (peach blossom), and to investigate molecular changes associated with its metabolic effects in a high-fat diet (HFD)-induced obesity mouse model. Methods: Male C57BL/6N mice were fed an HFD and orally administered HT099 (50 or 100 mg/kg) or the positive control orlistat (40 mg/kg) for 12 weeks. Body weight, adipose tissue accumulation, food efficiency ratio, glucose tolerance, serum lipid profiles, and hepatic gene expression related to lipid metabolism were evaluated. Results: HT099 supplementation significantly attenuated body weight gain and reduced white adipose tissue accumulation while improving food efficiency ratio. HT099 also ameliorated HFD-induced glucose intolerance and favorably modulated serum lipid profiles, including reduced triglyceride levels, increased HDL-cholesterol levels, and improved non-HDL cholesterol indices. At the molecular level, HT099 administration was associated with an increased hepatic AMPKα1 mRNA expression and decreased expression of adipogenic and lipogenic genes, including C/EBPα, PPARγ, FAS, and SREBP-1c. Conclusions: These findings indicate that HT099 exerts anti-obesity effects in HFD-induced obese mice, accompanied by improvements in lipid and glucose metabolism and changes in adipogenesis- and lipogenesis-related gene expression. Collectively, the results support the potential of HT099 as a natural bioactive agent for obesity management.