Aim: To determine the effectiveness of Anti-Acne from the methanol extract of dragon fruit peel (Hylocereus polyrhizus) by In vitro and In vivo assay. Methods: This study was an experimental study using disc diffusion and microdilution methods as in vitro methods. Meanwhile, the topical application of dragon fruit peel extracts to P. acne-injected rats by In vivo method. Results: Dragon fruit peels methanolic extract had MIC and MKC values ​​of 50 mg/ml by In vitro assay. In addition, the dragon fruit peels methanolic extract as a gel showed significant improvement in acne vulgaris lesions after 7-14 days of extract administration (p-value < 0.05). The lesion improvement was demonstrated by decreasing the size of the lesion. It was supported by the regeneration of the epidermal structure of all groups that received dragon fruit peels extract gel compared to the control group that only received gel base. Conclusion: Dragon fruit peels methanol extract has an antiacne effect in a physically stable gel form.