Horse chestnut (Aesculus hippocastanum L.) is a specific tree of Eastern Europe, including Balkan Mountains. It is an ornamental tree, but its seeds are valuable for their important content of triterpenoid saponins, especially β-aescin (or β-escin). Other biologically active compounds found in A. hippocastanum are flavonoids, anthocyanidins and their glycosides. In this review, the biologically active compounds from Aesculus species, especially A. hippocastanum, have been reported. The classification, extraction and purification methods of biologically active compounds from these species were emphasized. Moreover, the main biological activities of both Aesculus extracts and purified compounds, including the treatment of chronic venous insufficiency, vascular protection and venotonic effect, as well as anti-inflammatory and antioxidant activities, were reviewed.