Despite new treatment methods, upper gastrointestinal bleeding remains challenging. Samen-ista emulsion is a new agent based on traditional medicine with coagulant properties. The efficacy and safety of Samen-ista were assessed in cutaneous and mucosal bleeding animal models. Coagulant properties of Samen-ista were evaluated using mice tail bleeding assay, marginal ear vein and upper gastrointestinal mucosal bleeding times in rabbits. After 7 days, clinical signs, mortality and end-organ (kidney, liver, lung, brain and gastric mucosa) histopathological changes were also examined. Samen-ista dose-dependently decreased mean cutaneous tail (128 vs. 14 s) and marginal ear vein (396 vs. 84 s) bleeding times. Rabbit's upper gastrointestinal bleeding time was also significantly decreased (214 vs. 15.8 s) upon Samen-ista local endoscopic application. Treatment with Samen-ista for 7 days did not cause any mortality, abnormal signs of bleeding, changes in appetite or significant histopathologicl changes. Samen-ista emulsion is well tolerated and highly effective in achieving hemostasis in cutaneous and mucosal bleeding animal models.