Orlistat, which has a new mechanism of action, is currently the only approved weight-loss drug in China. In addition to controlling body weight, orlistat can significantly improve blood glucose, blood pressure, dyslipidemia, adiponectin, insulin concentration and other obesity-related biochemical indicators in patients with overweight/obese. Recently, orlistat was approved for weight management in patients with polycystic ovary syndrome. Although there are clinical trials supporting the good weight loss efficacy of orlistat, its long-term safety and effectiveness in obesity-related diseases still need to be further determined. This article provides a brief review of the new progress in the clinical efficacy and safety of orlistat, aiming to provide a reference for the more rational drug application.