Objective To study the analgesic and anti-inflammatory activities of water extract from Smilax siderophylla and its safety. Methods An acute toxicity assay was performed to observe the toxicity response and death in mice. Analgesic effect was observed by acetic acid-induced writhing response in mice. Anti-inflammatory effects were evaluated by models of auricle edema in mice and cotton pellet granuloma in rats. Results The minimum lethal dose of water extract from Smilax siderophylla was 12.15 g/kg and the maximum tolerated dose was 10.94 g/kg. The mainly toxicity response was diarrhea. Compared with the vehicle control group， the water extract from Smilax siderophylla 3 g/kg group could significantly reduce the numbers of writhing and reduce the auricle edema in mice. At the same time， it could obviously reduce the granuloma hyperplasia in rats. Conclusion The water extract from Smilax siderophylla has markedly analgesic and anti-inflammatory activity.