We have investigated potential antioxidant properties of the clinically relevant bile acid UDCA, which reaches therapeutic concentrations up to 0.09 and 29mM, respectively, in human plasma and bile. UDCA was an excellent scavenger of OH generated by FeCl 3 -EDTA, H 2 O 2 and ascorbate in the deoxyribose oxidation test, showing ic m i n and ic 5 0 values of 0.02 and 0.2mM, respectively, and a second-order rate constant for reaction with OH of 2+/-0.1x10 1 0 M - 1 s - 1 . Notably, the drug could enhance at 1.5mM concentration the antioxidant capacity of human bile against OH -induced deoxyribose oxidation. UDCA also showed antioxidant effects in the deoxyribose test performed with nonchelated iron ions, such as Fe 2 + plus H 2 O 2 (ic m i n : 7mM, ic 5 0 : 20mM) or Fe 3 + plus H 2 O 2 and ascorbate (ic m i n : 0.3mM, ic 5 0 : 5mM), and inhibited ferrozine-Fe 2 + and desferrioxamine-Fe 3 + complexes formation with ic 5 0 values of, respectively, 12 and 0.3mM, indicating that the drug interacts more with iron(III) than with iron(II). Moreover, UDCA significantly inhibited phospholipid liposome peroxidation induced by the OH -generating system FeCl 3 -EDTA, H 2 O 2 and ascorbate (ic m i n : 0.75mM, ic 5 0 : 3mM), and by peroxyl radicals generated in the aqueous phase by AAPH (ic m i n : 8mM, ic 5 0 : 14mM). UDCA, even at 25mM concentration, was ineffective on the lipoperoxidation mediated by Fe 2 + alone, but at the same concentration counteracted significantly that by Fe 3 + plus ascorbate, further pointing to its preferential antioxidant interaction with iron(III).In conclusion, UDCA has direct antioxidant properties, which are especially relevant against Fe 3 + - and OH -dependent biomolecular oxidative damage; such properties are evident at therapeutically relevant drug concentrations, suggesting that UDCA could act as an antioxidant in vivo.