Dioscorea plants have been widely used as traditional medicine and food for health benefits. Several therapeutic properties such as anti-cough, anti-diabetic, anti-diarrhea, and anti-cancer have been reported. Although the steroidal saponins (such as diosgenin) account for some of Dioscorea’s activity, there is little information on the effective components. We have shown here that water yam (Dioscorea alata L.) aqueous extract (YAE) inhibited the H2O2-CuSO4 induced damage of calf thymus DNA, and protected cultured human lymphoblastoid cells from CuSO4-induced DNA damage. This aqueous extract exhibited a major absorption peak at 260 to 262 nm. Upon the addition of CuSO4, the absorption peak was shifted to 236 nm and it was sensitive to the divalent ion chelator EDTA. The aqueous extract of YAE was also capable of dissociating the complex formation of Cu (II) with tetramethyl murexide (a copper indicator). Thin layer chromatography indicated that it contains one major and several minor anisaldehyde-, sulfuric acid-reactive and highly polar compounds. Based on these findings, we suggest that water-soluble mucilaginous polysaccharides within YAE are likely the effective compounds/candidates, which carry copper-chelating activity, and protect DNA against H2O2-CuSO4 combination or CuSO4 alone. Key words: Water yam (Dioscorea alata L.), Fenton reaction, metal chelating activity, DNA damage protection, antioxidant.