Hyperuricemia (HUA) is a metabolic disorder that occurs due to the overproduction or under-excretion of uric acid (UA) and is directly linked to the development of many life-threatening diseases. There is a growing interest among many researchers regarding how to overcome the encumbrance of HUA because conventional drugs are associated with multiple side effects. Thus, the present project has been designed to utilize flavonoids and chlorogenic acid-enriched stevia residue extract (STVRE) to combat HUA. The results show that supplementation with STVRE (200 and 400 mg per kg bw) inhibits the XOD enzyme in serum, duodenum, jejunum, and ileum tissues. Moreover, UA levels in the STVRE groups were also significantly (p < 0.05) decreased in serum, duodenum, jejunum, and ileum tissues and juices. STVRE also improved the intestinal morphology and oxidative biomarkers in duodenum, jejunum, and ileum tissues. Protein and mRNA expressions of ABCG2 were upregulated, whereas GLUT9 was downregulated in the STVRE-treated groups as compared with the model control group. The supplementation of STVRE significantly attenuated hyperuricemia and oxidative stress, upregulated ABCG2 and downregulated GLUT9 (protein and mRNA) expression in hyperuricemic mice. The results of our study revealed that the by-product of stevia has the potential to combat hyperuricemia, and can be used as a functional ingredient in the development of nutraceutical products.