Objective: Study the mechanism of ginsenoside Rg(1) in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography-mass spectrometry. Results: Ginsenoside Rg(1) significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg(1) improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg(1) down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg(1) significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg(1) markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg(1) ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats.