ABSTRACT: Loquat (Eriobotrya japonica) is a popular fruit and medicinal plant. Here, a high-quality draft genome of the E. japonica ‘Big Five-pointed Star’ cultivar that covers ~98% (733.32 Mb) of the estimated genome size (749.25 Mb) and contains a total of 45,492 protein-coding genes is reported. Comparative genomic analysis suggests that the loquat genome has evolved a unique genetic mechanism of chromosome repair. Resequencing data from 52 loquat cultivars, including 16 white-fleshed and 36 yellow-fleshed variants, were analyzed, and the flower, leaf, and root metabolomes of ‘Big Five-pointed Star’ were determined using a UPLC-ESI-MS/M system. A genome-wide association study identified several candidate genes associated with flesh color in E. japonica, linking these phenotypes to sugar metabolism. A total of 577 metabolites, including 98 phenolic acids, 95 flavonoids, and 28 terpenoids, were found, and 191 metabolites, including 46 phenolic acids, 33 flavonoids, and 7 terpenoids, showed no differences in concentration among the leaves, roots, and flowers. Candidate genes related to the biosynthesis of various medicinal ingredients, such as phenolics, flavonoids, terpenoids, and polysaccharides, were identified. Some of these genes were confirmed to be members of expanding gene families, suggesting that the high concentrations of beneficial metabolites in loquat may be associated with the number of biosynthetic genes in this plant. In summary, this study provides fundamental molecular insights into the nutritional and medical properties of E. japonica.