Licorice, the root extract of Glycyrrhiza glabra L., is used as a medicine for various diseases. Anti‐inflammatory as well as anti‐allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, β‐glycyrrhetinic acid. β‐Glycyrrhetinic acid has a steroid‐like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of β‐glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that β‐glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC₅₀=35 μm), whereas no inhibitory activity was observed towards the alternative pathway (IC₅₀>2500 μm). The anticomplementary activity of β‐glycyrrhetinic acid was dependent on its conformation, since the α‐form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that β‐glycyrrhetinic acid acts at the level of complement component C2.