The crude flavonoids and saponins of Ilex cornuta leaves not only inhibited XOD activity in vitro, but also significantly controlled XOD activity and reduced UA level in hyperuricemia mice in vivo. One of the potential mechanisms was to regulate UA level in vivo by regulating ABCG2, GLUT9, and URAT1 transporters directly related to UA transport, thus achieving the effect of intervening hyperuricemia. This study provided a preliminary experimental basis for the development of new drugs of Ilex cornuta leaves for treating hyperuricemia.