Triterpenoids derived from natural products can exert antihyperuricemic effects. Here, we investigated the antihyperuricemic activity and mechanism of quinoa bran saponins (QBSs) in hyperuricemic mouse and cell models. The QBS4 fraction, with the highest saponin content, was used. Fourier-transform infrared, high-performance liquid chromatography, and ultrahigh-performance liquid chromatography-mass spectrometry identified 11 individual saponins in QBS4, of which the main components were hederagenin and oleanolic acid. The QBS4 effects on hyperuricemic mice (induced by adenine and potassium oxonate) were then studied. QBS4 reduced the levels of uric acid (UA), serum urea nitrogen, creatinine, and lipids in mice with hyperuricemia (HUA) and decreased renal inflammation and renal damage. Molecular analysis revealed that QBS4 may alleviate HUA by regulating the expression of key genes involved in the transport of UA and by inhibiting the activation of the PI3K/AKT/NFκB inflammatory signaling pathway. In conclusion, QBS4 has promise for using as a natural dietary supplement to treat and prevent HUA.