Alpha mangostin, a natural xanthone derivative from mangosteen fruit pericarp, exhibits antiproliferative and apoptotic effects on different cancer cells by inhibiting cell cycle progression, inducing apoptosis, and modulating signaling pathways. However, this candidate is limited in medical treatment due to the poor water solubility. Nanoparticles have emerged as promising drug delivery systems to improve drug delivery efficiency but one of the problem of nanoparticles is the capability of endosomal escape. Therefore, pH-sensitive polymer nanosystems were utilized for targeted drug delivery, and enhanced efficacy by offering controlled release and endosomal escape capabilities. This study aimed to synthesize PEG- P(Asp-Hyd-Man) copolymer and create micelle for alpha mangostin delivery. The micelles were measured with particle size average of 80.2 ± 15 nm, and the PDI of 0.17. Additionally, the release behavior of alpha mangostin was examined in vitro that show pH-sensitive polymeric micelles rapidly release at pH 5.0 compared with the arterial pH 7.4. The findings of this study are significant in the development of an effective drug delivery system using alpha mangostin and other therapeutic agents.