Monosaccharides are polyhydroxyl compounds containing several chiral carbons, giving rise to tens of isomeric forms. Only minority of them are natural carbohydrates existing in nature abundantly, and most of them are rarely in nature, called rare sugars. These rare sugars attract increasing attention because of their low-calorie property and promising beneficial effects. Izumoring strategy has been established for linking all monosaccharides by three types of enzymes including ketose 3-epimerases, polyol dehydrogenases, and aldose isomerases. Recently, more attention has been paid on the Izumoring of hexoses, especially the D-zone hexoses. So far, at least ten isomerases have been used for the isomerization reactions between D-aldohexoses and D-ketohexoses. In this article, the interconnections and potential physiological effects of D-ketohexoses and D-aldohexoses are summarized, the D-zone hexose Izumoring is shown by giving the exact biocatalysts, and importantly, the isomerases for D-hexose biotransformation are reviewed in detail.