Objectives <p>To investigate the relationship between individual urinary phytoestrogen metabolites and hyperuricemia (HUA), as well as the potential impact of a mixture of these metabolites on HUA.</p> Methods <p>This cross-sectional study included a total of 9253 participants, with data sourced from the National Health and Nutrition Examination Survey (NHANES). Urinary levels of daidzein, o-desmethylangolensin (O-DMA), equol, genistein, enterodiol, and enterolactone were measured to assess exposure to urinary phytoestrogen metabolites. HUA was defined as the study outcome. First, weighted logistic regression and smoothed curve fitting were used to analyze the relationships between individual urinary phytoestrogen metabolites and HUA. Subsequently, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) models were used to explore the comprehensive effects of the six phytoestrogen metabolites on HUA.</p> Results <p>The prevalence of HUA in this study was approximately 18.33%. Weighted logistic regression analysis indicated that urinary daidzein, O-DMA, equol, and enterolactone were associated with a reduced risk of HUA. The study further identified threshold effects of daidzein, O-DMA, and equol on the risk of HUA. WQS, qgcomp, and BKMR models revealed that mixed metabolites of urinary phytoestrogens were negatively correlated with HUA risk, with equol and enterolactone being the main contributors. A comprehensive comparison of the results from these models demonstrated high stability and consistency.</p> Conclusion <p>Mixed urinary phytoestrogen metabolites were inversely associated with the risk of HUA, with equol and enterolactone serving as the primary contributing factors. This observational study provides a basis for public health strategies but cannot establish causality.</p> <p><Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="justify" colname="c1" colnum="1" /> <colspec align="justify" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> <p><b>Key Points</b></p> <p>• <i>Large-scale population studies have shown that plant estrogen metabolites (daidzein, o-desmethylangolensin, equol, and enterolactone) are significantly inversely associated with hyperuricemia (HUA) risk. Saturation effects were observed for daidzein, o-desmethylangolensin, and equol.</i></p> <p>• <i>This study confirms that mixed exposure to these metabolites reduces HUA risk, mainly due to equol and enterolactone.</i></p> <p>• <i>Promoting public health policies to harness plant estrogens’ benefits could improve population health.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>