«Abstract: Acne vulgaris is one of the most common dermatologic disorders affects people of all races and ethnicities and has many adverse effects on the quality of life. The increased bacterial resistance to antibiotics has reduced the effectiveness of treatment with these agents. There is an increasing focus on the involvement of oxidative stress in the pathophysiology of acne. This study investigates the effect of N-acetylcysteine (NAC) as an antioxidant in the treatment of acne vulgaris. This systematic review was conducted through a search in databases such as Science Direct, PubMed, Scielo, and Medline using keywords including acne vulgaris, anti and NAC, and all the keywords associated with each of the subtitles. The factors affecting the occurrence and expansion of acne include increased sebum synthesis, hyperkeratinization of pilosebaceous units, colonization with Propionibacterium acne, and increased release of inflammatory mediators and ROS. Studies have shown that glutathione stimulation following the administration of NAC increases glutathione levels for the detoxification of oxygen-free radicals. Moreover, NAC prevents the synthesis and release of inflammatory cytokine such as TNF-α, IL-8, IL-6, MP9, and IL-1β and has shown antibacterial activities against important bacteria including E. coli, S. epidermidis, Pseudomonas, and Klebsiella. This medication has anti-proliferative effects and is also used for excoriation and PCOD. The results of the present study showed the beneficial effects of using NAC in patients with acne vulgaris in terms of the disease complications and comorbidities. Given its diverse functional mechanisms, this medication can be used to treat acne and its consequences.»