White pepper seeds (Piper nigrum L.) have main alkaloid compound, it is piperin. Piperin has several pharmacological effects such as enhancing the enzyme digestion in the pancreas (lipase, amylase and protease), antidepressants, anti-inflammatory,anti-arthritis, anti-inflammatory, hepatoprotective, antibacterial and stimulating enzymes in the intestine. This study aimed to determine the subchronic toxicity of piperine on body weight, gastric ulcer score and mucosal damage in gastric histology of mice balb/c. This research used post-only control group method. White pepper seeds are extracted using the socletation method. This subchronic toxicity were carried out on 30 male mice, 35-45 grams, 2-3 months. Mice were divided into 5 groups consisting of 1 control group and 4 treatment groups with a doses of 17.5 mg/KgBB, 35 mg/KgBB, 70 mg/KgBB and 140 mg/KgBB which were given piperine orally for 21 days. Mice weighed once a week. Gaster organs of the mice were dissected and do scoring of the number and severity of the ulcer. Gaster was fixed with formalin 10% and HE staining. Gaster preparations were observed under microscope with 10x and 40x magnification and then do scoring damage to mucosal integrity. Data on body weight of mice were analyzed using the Oneway ANOVA and Post-Hoc test and the result of ulcer scores and mucosal damage were analyzed using the Kruskal Wallis and Mann-Whitney tests. Giving piperine for 21 days caused a decrease in body weight of mice with a significance value p>0.05 or no significant difference between groups. Macroscopic observations of piperine dosages 17.5 mg / KgBB, 35 mg / KgBB, 70 mg / KgBB and 140 mg / KgBB caused gastric histopathological changes such as redness, bleeding and ulcers. Statistic result of the number of ulcers and ulcer severity is p <0.05 or included significant differences between the control and treatment groups. Microscopically (histology) shows gastric histopathological changes such as desquamation, erosion and epithelial ulceration. The severity increases with increasing dosage given. Statistic result of mucosal damage is p <0.05 or there is a significant difference between the control and management groups.