Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism, often accompanied by inflammation. It is characterized by an abnormal elevation in uric acid (UA) levels. In our investigation, the combined treatment with Lactiplantibacillus plantarum DY1 and quercetin suppressed the activity of xanthine oxidase and adenosine deaminase, decreased the levels of UA, tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-β), downregulated gene expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and upregulated organic anion transporter 1 (OAT1) and ATP-binding cassette transporter subfamily G member 2 (ABCG2). The combination increased the abundance of Lactobacillus and decreased the abundance of norank_f_norank_o__Clostridia_UCG-014 and Roseburia. Metabolomics analysis revealed that the combination of probiotics and quercetin exhibited distinct metabolic pathways compared to their individual administrations. When compared to probiotics alone, the combination led to alterations in glutathione metabolism (oxidized glutathione and glutathione) as well as sphingolipid metabolism (sphingosine and sphinganine). When compared to quercetin alone, the combination resulted in variations in tryptophan metabolism (indole-3-acetamide, 5-hydroxy-L-tryptophan, indoleacetaldehyde, 3-(3-indolyl)-2-oxopropanoic acid, 3-indoleacetic acid and 3-methylindole) along with purine metabolism (UA, xanthosine, cyclic adenosine monophosphate (cAMP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP)). The subsequent fecal microbiota transplantation proved that the effect of the combination on reducing UA levels was mediated by the gut microbiota. Therefore, this new combination can be considered a promising adjuvant therapy capable of synergistically alleviating hyperuricemia.