In an attempt to find a natural antiobesity agent, this study was designed to evaluate the antiobesity activity of a novel herbal preparation Mubella composed of refined konjac meal and mulberry leaf extract in high-fat diet plus olanzapine-induced obese mice. After eight-week oral administration of the test materials to mice, the body weight gain, abdominal fat mass, and serum lipid profile were measured. Additionally, hepatic steatosis and injury were evaluated in the present study. Our results indicated that Mubella can suppress body weight gain and lower BMI in obese mice. Significant decreases in visceral abdominal fat mass were observed in Mubella-treated groups compared with the untreated obese group. Furthermore, the oral administration of Mubella improved significantly serum lipid profile, and prevent liver injury by reducing fat accumulation decreasing transaminase activities. These findings suggest that Mubella holds great promise for a novel herbal preparation with antiobesity activities, preventing body fat accumulation and altering lipid metabolism.