Phenyl sulfate is a gut microbiota-derived metabolite of tyrosine and a recognized uremic toxin. At a concentration of 30 µM, phenyl sulfate reduces the survival of differentiated human urinary podocyte-like epithelial cells (HUPECs), decreases intracellular glutathione (GSH) levels, and induces mitochondrial dysfunction. In a db/db mouse model of diabetes, phenyl sulfate administered at a dose of 50 mg/kg induces podocyte damage and albuminuria. Elevated plasma levels of phenyl sulfate are correlated with the progression of albuminuria in patients suffering from diabetic kidney disease, highlighting its role as a biomarker and potential therapeutic target.