This study seeks to investigate the therapeutic effects of Si Miao San (SMS) on hyperuricemia and its underlying mechanisms, particularly focusing on the role of intestinal flora. The key components of SMS were identified using high-performance liquid chromatography (HPLC). To establish a rat model of hyperuricemia, an intraperitoneal injection of potassium oxonate was performed, followed by oral administration of various concentrations of SMS. The study evaluated the status of hyperuricemia, renal pathology, xanthine oxidase (XO) activity, and intestinal flora. Utilizing HPLC, we identified five active components of SMS. Following SMS intervention, there was a significant reduction in serum levels of uric acid (UA), blood urea nitrogen, and creatinine, accompanied by an increase in urine UA levels in rats with hyperuricemia. Distinct pathological injuries were evident in the renal tissues of hyperuricemic rats, and these were partially alleviated following SMS intervention. Moreover, SMS exhibited a dose-dependent reduction in XO activity both in the serum and hepatic tissues. Notably, SMS contributed to an enhancement in the diversity of intestinal flora in hyperuricemic rats. The intervention of SMS resulted in a reduction in the abundance of certain bacterial species, including Parabacteroides johnsonii, Corynebacterium urealyticum, and Burkholderiales bacterium. This suggests that SMS may exert anti-hyperuricemia effects, potentially by modulating the composition of intestinal flora.