Background: The properties of mangosteen skin as anti-inflammatory have been described by manyresearchers both in vitro and in vivo. Over the past few years, mangosteen peel extract is used as a naturalherbal remedy either orally or topically. However, the potential toxicity of extracts and formulationscontaining mangosteen peels is still a matter of little concern.Objective: To prove that mangosteen skin extract is safe to use as natural herbal medicine. Methods:Experiments with laboratory tests of microbiological tests and acute toxicity tests with samples of 30 Balb /C mice aged 8-10 weeks weight 25-35 g, divided into 6 groups in which 5 groups of intervention (givingmangosteen skin extract) with different dose (5, 50, 300, 2000 and 5000 mg / kgBB) and 1 control group.Parameters observed included weight, motor activity, salivation, respiration, defecation, urination,piloerection every day for 14 days while the observed organ was liver. Behavioral data and organ testresults were used to evaluate the toxic effects of mangosteen skin extract. Data was analyzed with ANOVAand Post Hoc Test.Results: Most subjects' mean body weight from day 0 to day 14 tended to stabilize with a slight increase ordecrease of less than 1%. The results of observation for 14 days after the intervention to each group therewas no death and no effect on the motor system, saliva, respiration, defecation, urination and piloerectionand did not happen itch allergies. Based on Post Hoc Test (LSD), there was no significant difference inmean liver weight group with highest dose (5000 mg / kgBB) and control group.Conclusion: Extract of mangosteen skin with dosage ? 5000 mg/kg BW is not toxic and safe to use asnatural herbal medicine.