α-Mangostin, initially identified in 1855, is a xanthone derivative compound predominantly located in the pericarp of the mangosteen fruit (Garcinia mangostana L). This compound is known for its beneficial properties as an antioxidant and anti-inflammatory agent, still holding promise for potential benefits in other related pathologies. In the investigative process, computational studies have proven highly valuable in providing evidence and initial screening before progressing to preclinical and clinical studies. This review aims to present the pharmacological findings and mechanisms of action of α-mangostin based on computational studies. The compilation of this review is founded on the analysis of relevant articles obtained from PubMed, Scopus, and ScienceDirect databases. The study commences with an elucidation of the physicochemical characteristics, drug-likeness, pharmacokinetics, and toxicity profile of α-mangostin, which demonstrates that α-mangostin complies with the Lipinski's Rule of Five, exhibits favorable profiles of absorption, distribution, metabolism, and excretion, and presents low toxicity. Subsequent investigations have revealed that computational studies employing various software tools including ArgusLab, AutoDock, AutoDock Vina, Glide, HEX, and MOE, have been pivotal to comprehend the pharmacology of α-mangostin. Beyond its well established roles as an antioxidant and anti-inflammatory agent, α-mangostin is now recognized for its pharmacological effects in Alzheimer's disease, diabetes, cancer, chronic kidney disease, chronic periodontitis, infectious diseases, and rheumatoid arthritis. Moreover, α-mangostin is projected to have applications in pain management and as a potent mosquito larvicide. All of these findings are based on the attainment of adequate binding affinity to specific target receptors associated with each respective pathological condition. Consequently, it is anticipated that these findings will serve as a foundation for future scientific endeavours, encompassing both in vitro and in vivo studies, as well as clinical investigations, to better understand the pharmacological effects of α-mangostin.