Acne vulgaris (AV) is a chronic inflammation of pilosebaceous unit that is common in teenagers. According to its severity degree, AV can be categorized as mild, moderate, and severe. One of its alternative therapies on severe AV is isotretinoin. Oxidative stress affects the formation of acne vulgaris, therefore the antioxidant is considered as an additional therapy. Glutathione is of the antioxidants which has a protective effect on oxidative stress. Two male patients age of 20 years old suffered from severe AV for approximately a year. Both of the patients had several therapies but had not improved, by which one patient being treated with the combination of isotretinoin and glutathione and the other with isotretinoin alone for 4 weeks. Inflammation is one of the factors on the pathogenesis of AV. Isotretinoin as the first retinoid generation which functions as antiinflammation and immunomodulator, is one of the alternative therapies on mild AV. Oxidative stress is one of the causes of inflammation on AV. Glutathione is an antioxidant which functions as a protection to the oxidative stress. There is an improvement on severe-degree AV which treated with the combination of isotretinoin and glutathione as well as with isotretinoin alone.