Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet.

Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor of pancreatic lipases isolated from the bacterium Streptomyces toxytricini. However, due to its relative simplicity and stability, orlistat was chosen over lipstatin for development as an anti-obesity drug.

The effectiveness of orlistat in promoting weight loss is definite but modest. Pooled data from clinical trials suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about 2–3 kilograms (4–7 lb) more than those not taking the drug over the course of a year. Orlistat also modestly reduces blood pressure and appears to prevent the onset of type 2 diabetes, whether from the weight loss itself or other effects. It reduces the incidence of diabetes type II in people who are obese around the same amount that lifestyle changes do.

Benefits aside, however, orlistat is noted for its gastrointestinal side effects (sometimes referred to as treatment effects), which can include steatorrhea (oily, loose stools). They decrease with time, however, and are the most frequently reported adverse effects of the drug. In Australia, the United States and the European Union, orlistat is available for sale without a prescription. Over-the-counter approval was controversial in the United States, with consumer advocacy group Public Citizen repeatedly opposing it on safety and efficacy grounds. Generic formulations of orlistat are available in some countries. In Australia it has been listed as an S3 medication, available from a pharmacist without a prescription, since 2000.