A hot water extract of the Australian native sarsaparilla Smilax glyciphylla Sm. (Smilaceae) inhibited peroxidation of phosphatidylcholine liposomes initiated by Fe(2+)/ascorbate (IC50, 10 microg/mL) and AAPH (IC50, 33 microg/mL) in vitro. It also inhibited deoxyribose degradation and quenched chemically generated superoxide anion (IC50, 50 microg/mL). Reactivity towards ABTS (2,2'-azinobis(3-ethylbenzothiazoline 6-sulphonate) radical cation was equivalent to 48.4 mM TROLOX, the water soluble alpha-tocopherol analogue. Smilax glyciphylla is a rich source of the dihydrochalcone glycyphyllin. Given the reported level of activity it is unlikely that glycyphyllin would provide direct antioxidant protection in tissues affected by oxidative stress. However, consuming Smilax glyciphylla as a tea may be sufficient to reduce oxidative damage in the gastrointestinal tract. It is also possible that glycyphyllin is metabolised and adsorbed as phloretin, a compound with known anticancer properties. These findings indicate that further studies of the chemopreventative properties of Smilax glyciphylla is warranted.