Flavonoids and phenolic acid metabolites excreted in human urine after ingestion of Sideritis scardica decoction with characterized polyphenolic composition were studied. A feeding study was carried out with 10 human volunteers, and urine samples were collected for 24 h after ingestion of the Sidertis decoction. Polyphenol metabolites were identified and quantified in urine samples by HPLC with tandem mass spectrometric detection. Thirty-one different metabolites of hypolaetin, methylhypolaetin, isoscutellarein, methylisoscutellarein, and apigenin and 32 phenolic acid metabolites were detected and quantified using a method validated for this purpose. The urinary excretion of polyphenol metabolites corresponded to 5% (n/n) of the intake of polyphenols from the Sideritis decoction. Flavonoid metabolites were dominant in urine samples with 87-94% of total polyphenolic metabolites content. The most abundant metabolites were methylhypolaetin and methylisoscutellarein glucuronides. Urinary excretion of isoscutellarein (35.61%) was 10 times higher than that of hypolaetin (3.67%). Apigenin also showed high urinary excretion (32.46%).