Shiikuwasha (Citrus depressa Hayata) is produced in the northern area of the main Okinawa island, the southern most region of Japan, and is a typical Japanese citrus along with Tachibana (Citrus tachibana). The seed of Shiikuwasha contains high concentration of limonoid glucosides, including limonin glucoside and nomilin glucoside, which has anti-tumor activity. Synephrine, a well-known enhancer of lipid metabolism, is also present in the fruit peel. The most notable feature of Shiikuwasha, among citrus fruits harvested commercially in Japan, is its high concentration of polymethoxylflavones, such as nobiletin (NBL), tangeretin and sinensetin. These are present in the peel, where NBL is predominant. Many studies have demonstrated that NBL possesses various biological properties such as anti-carcinogenic, anti-inflammatory and hepatoprotective activities. The ingestion of Shiikuwasha paste decreases plasma glucose level in laboratory animals, such as mouse and rat, as well as human volunteers. Study of the metabolism, by animal and human liver microsomes and cytochrome P450 of NBL shows the presence of 4’-OH, 7-OH, 6-OH metabolites, as well as the novel metabolites 3’ and 4’-diOH NBL. These results indicate that Shiikuwasha is an attractive foodstuff from the perspective of health promotion. Furthermore, in order to maintain Shiikuwasha authenticity, methods distinguishing between Shiikuwasha and Calamondin were developed using a unique phloretin glucoside and certain polymethoxyflavones as chemical markers, as well as Shiikuwasha chloroplast DNA.