In this study, we optimized the production of rare sugars, such as tagatose, using galactose aqueous solution and eggshell powder as raw materials through isomerization by microwave heating. Similar to the conventional subcritical water treatment, isomerization of galactose to tagatose proceeded efficiently by the microwave heating, achieving a maximum tagatose yield of 16 mol% after a treatment at 600 W for 210 s. A high tagatose selectivity (up to 76%) was obtained in the early reaction stage. However, as the treatment time increased, byproducts (organic acids and ketones) accumulated, causing a decrease in both the yield and the selectivity of tagatose. Analysis of the byproducts suggested a reaction pathway in which galactose and tagatose decompose into ketones and organic acids through the pathways such as retro-aldol condensation. Furthermore, increasing the initial galactose concentration improved weight-based concentrations of the produced rare sugars although their molar yields decreased. Based on these results, microwave heating treatment was concluded to be an effective method for the production of tagatose in a short time, with optimization of microwave output, time, and feedstock concentration being key to achieving high yields.