It is generally agreed that reactive oxygen species (ROS) are contributed to skin aging, skin disorders and skin diseases. Skin possesses an extremely efficient antioxidant system. This antioxidant activity is donated by two systems: antioxidant enzymes, and small molecules which can scavenge ROS by donating electrons. No gene-encoded secreted ROS scavengers have been reported. Amphibian skin is a multifunctional organ acting as defence, respiration and water regulation although it seems susceptible. Amphibian skins are easy to be harmed by biological or non-biological attacks such as microorganism infection or radiation injury. Among vertebrates, skins of amphibian are exposed to more dangers of radiation injury than others. Radiation toxicity occurs either by direct attacking the genetic material and/or by generating ROS. In addition, amphibian skin respiration and inflammatory response also induce ROS generation. It is rational to hypothesize that amphibian skins should have potent free radical scavenging and radioprotective ability for their survival. Rana pleuraden is distributed in Southwest of China, which lives in sub-tropical plateau (altitude around 2300 m) where there is strong ultraviolet radiation and long sunshine time. By peptideomics and genomics approaches, a large amount of antioxidant peptides belonging to 11 different groups with variable structures were isolated from the skin secretions of R. pleuraden. Their free radical scavenging and anti-inflammatory abilities were studied. All of these peptide share highly homologous prepro-regions although mature antioxidant peptides are with very divergent primary structures, suggesting the possibility of a common ancestor. Some peptides were also found to have multi-functional properties, such as combined antioxidant, anti-inflammatory and antimicrobial activities. According to our knowledge, no gene-encoding specific antioxidant peptides have been reported except metallothionein. Our work possibly reveals a new skin antioxidant system. The current work also provides a large amount of peptide candidates with medical-pharmaceutical significance.