Gut microbiota is associated with hyperuricemia progression and can be regulated by Lactobacillus plantarum. However, the role of Lactobacillus plantarum in hyperuricemia is still unknown. Thus, we constructed the mouse model of hyperuricemia using potassium oxonate and hypoxanthine treatment to explore the effects of Lactobacillus plantarum LLY-606 supplementation on the development of hyperuricemia. The results showed that Lactobacillus plantarum LLY-606 significantly reduced the level of serum uric acid through inhibiting uric acid secretion and regulating uric acid transport. We also found that Lactobacillus plantarum LLY-606 supplementation inhibited the inflammatory response and the activation of the TLR4/MyD88/NF-κB signaling pathway in mice. Microbiome sequencing and analysis suggested the successful colonization of probiotics, which could regulate intestinal flora dysbiosis induced by hyperuricemia. The abundance of Lactobacillus plantarum was significantly negatively correlated with hyperuricemia-related indicators. Notably, the functional abundance prediction of microbiota indicated that lipopolysaccharide biosynthesis protein pathways and lipopolysaccharide biosynthesis pathways were inhibited after the probiotic intervention. In conclusion, Lactobacillus plantarum LLY-606 can serve as a potential functional probiotic to affect the development of hyperuricemia through modulating gut microbiota, downregulating renal inflammation, and regulating uric acid metabolism.