Objectives. To compare the efficacy and safety profiles of systemic glutathione as a skin-whitening agent in adults from several randomized controlled trials (RCTs). Methods. This study is an evidence-based case report with literature search conducted on Clinical Key, Cochrane, Journal of the American Academy of Dermatology, Taylor and Francis Online, ScienceDirect, and PubMed databases. Three relevant RCTs were extracted and assessed for validity, importance, and applicability. Results. From 3 included trials, one of the studies opposed glutathione as a skin-whitening agent. However, the other two showed significant results only to some parts of the body or to certain age groups. As a skin-whitening agent, studies showed that glutathione yielded other cosmetic benefits as it may improve skin elasticity and reduce skin wrinkles. Furthermore, glutathione was well tolerated in oral preparations, but not in parenteral preparations. Conclusions. Highest-evidence literatures showed that glutathione is not beneficial enough as a skin-whitening agent as it was only effective in some parts of the body and did not elicit long-lasting effects. However, its safety profiles in oral preparations were well tolerated. More researches regarding the time needed for skin color to return to its original state following drug withdrawal need to be conducted as it is yet to be discovered.