Saponins are a group of compounds used in clinical practice in the management of several diseases. Escin is a natural mixture of triterpene saponins which mainly consist of several isoforms, in which the α- and β-escin are predominant. β-escin is the major active compound that exerts a therapeutic effect by relieving tissue edema, promoting venous drainage, and reducing inflammation. In this review, we describe the features of its glucocorticoid-like activity that could explain its clinical effects. Using PubMed, Embase Cochrane library and reference lists for articles published until October 01, 2020, we documented that escin is likely able to exert its anti-inflammatory and anti-edematous effects through a glucocorticoid-like activity, but without the development of glucocorticoid-like adverse drug reactions.