alpha-Mangostin (MGS), an anti-cancer compound, is a xanthone derivative and is extracted from the pericarps of mangosteen. MGS exhibits a variety of bioactivities, such as antioxidant, cytotoxic, anti-inflammatory, and antibacterial effects, as well as anticancer activity. However, MGS has not been approved for clinical use because of its poor bioavailability. There have been many efforts to solve this problem by use of drug carriers. Cyclodextrins (CDs) are well known as nontoxic and biodegradable drug carriers and can encapsulate MGS. In this study, we prepared CD-based nanoparticles (CDNPs) by a polyaddition reaction using epichlorohydrin and characterized them by dynamic light scattering and static light scattering coupled with fractionation. The encapsulation of MGS into CDNPs was examined, and we found that the loading ratio of MGS for CDNPs is much higher than that for CDs themselves. The cytotoxicity of the CDNP/MGS complex was examined, indicating the potential of CDNP as a carrier of MGS.