Background: Herbal medicine has been used for the treatment of obesity. Obesity is a very common global health problem, and it is known to be linked to metabolic diseases. Objective: To investigate on the anti-obesity effects of herbal medicines such as Rehmanniae radix (RR), Citrus unshiu peel (CUP), and Poria cocos wolf (PCW) in high-fat diet (HFD)-induced obese mice. Materials and Methods: C57BL/6 mice were fed a normal diet (ND) or an HFD for 6 weeks, and herbal medicines were administered orally three times a week for 8 weeks. Serum biochemical parameters were detected by measuring glucose, triglycerides, and total cholesterol. In addition, histological changes were observed in epididymal adipose tissues. Results: The RR, CUP, and PCW effectively lowered both the body weight and epididymal adipose tissue weight and reduced the adipocyte enlargement. In addition, we examined the serum biochemical profiles of HFD-induced obese mice to confirm the anti-obesity effects of RR, CUP, and PCW. Compared to the ND mice, the administration of RR, CUP, and PCW efficiently reduced the glucose, triglyceride, and total cholesterol serum levels in HFD-induced obese mice. Conclusion: These findings suggested that the herbal medicines, such as RR, CUP, and PCW, are potential novel agents for the prevention and treatment of metabolic diseases, especially obesity.