Glutathione, a potent antioxidant, has gained attention for its skin-lightening effects, leading to ethical debates. Social media influence has popularized its use in various skincare products such as under-eye creams, face masks, sunscreens, and moisturizers. Despite its popularity, scientific research on topical glutathione is limited.To perform a review of existing literature on the safety and efficacy of topical glutathione.A PRISMA-guided systematic review was conducted using PubMed and MEDLINE databases with search terms "glutathione" AND "topical" AND "skin" OR "dermatology." From 446 articles, only clinical trials on topical glutathione were included, excluding reviews, animal studies, and research on oral or intravenous glutathione. Five clinical trials met the inclusion criteria.Studies suggest glutathione may improve hyperpigmentation and provide antioxidant advantages. A glutathione amino acid precursor (GAP) blend increased the glutathione reduced monomers (GSH) oxidized dimers glutathione disulfide (GSSG) ratio, a surrogate measure for oxidative damage repair capacity. S-acyl glutathione 2% cream significantly reduced ultraviolet-induced erythema (p=0.0003). A 2% oxidized glutathione lotion decreased the melanin index (p<0.05), total epidermal water loss (TEWL) (p<0.05), and wrinkles (p<0.01). Combination creams with glutathione also showed benefits, though tolerability was varied. Safety data is limited and warrants further exploration.Topical glutathione shows promise for dermatological applications. Further randomized controlled trials are necessary to fully evaluate its efficacy in hyperpigmentation, TEWL, skin elasticity, and ultraviolet (UV) damage. Additionally, ethical considerations regarding its use as a skin-bleaching agent must be addressed to avoid reinforcing structural racism and healthcare disparities.