Glucosylglycerols (GGs) are known as compatible solutes accumulated by some bacteria including cyanobacteria as well as higher plants for their adaptations to salt or desiccation stresses. Since being identified in Japanese sake, their physiological effects and potential applications on human health cares have been explored in the following 15 years. Several different synthesis methods have been successively developed for the production of GGs. However, the efficiency of GG synthesis, especially biological synthesis, is still low. With the recent advances in genome sequencing and synthetic biology tools, systematical screening of enzyme candidates and metabolic engineering approaches is necessary for improving GG synthesis efficiency. In this review, we will summarize GG structure information, protective effects on human skin and digestive system as well as industrial enzymes, together with their synthesis by chemical, enzymatic, and biological in vivo approaches in detail, and provide some prospects on improving GG production.