Hyperuricemia (HUM) is a major risk factor for the development of gout. The traditional Chinese medicine (TCM) complex prescription Tongfengxiaofang (TFXF) is based on the theory of TCM and is composed of a variety of TCMs for the treatment of gout. To study the therapeutic effect of TFXF on HUM mice and the mechanisms by which it exerts a therapeutic effect, the biochemical indexes were measured and q-PCR technique as to evaluate the therapeutic effect of TFXF. In addition, plasma metabolomics analysis was carried out based on UPLC-Q-TOF/MS to evaluate the characteristics of metabolic spectrum changes. TFXF significantly down-regulated the content of UC, BUN, Cr in serum and the concentration of XOD in liver of HUM mice. In addition, TFXF significantly inhibited the overexpression of URAT1, GLUT9 and up-regulated the expression of OAT1 in the kidney of HUM mice. A total of 152 metabolites were identified and 11 key biomarkers were further selected from these pathways to understand the mechanism of TFXF on the Arginine biosynthesis, Galactose metabolism, Pyrimidine metabolism, Glycerophospholipid metabolism, Tryptophan metabolism and the Citrate cycle (TCA cycle). Results of this confirmed the effect of TFXF on HUM and revealed the metabolic activity mechanism of this effect.