Glucocorticoids are steroid drugs that are used to treat various inflammatory diseases. However, the severity of their side effects limits their application. In this study, we showed that ginsenosides, which consist of a steroid structure conjugated to saccharide groups, mediate their anti-inflammatory effects in wounding tail zebrafish larvae depending on glucocorticoid receptors. Ginsenosides show dramatically reduced side effects on glucose and cortisol levels, growth, and tissue regeneration in zebrafish larvae. Interestingly, Glucosylceramidase beta 2 (Gba2), which was strongly induced by inflammation in the zebrafish model, mediates the cleaving of the saccharide groups from the ginsenosides only in inflamed tissues and restricted Gr activation to inflamed sites. Subsequently, we have developed a novel way of modifying the structure of glucocorticoid drugs. We attached the disaccharide gentiobiose to prednisolone. Glycosylation dramatically decreased GR activities and made glucocorticoids inactive compounds. However, upon the induction of GBA2 after inflammation stimuli (TNF-α), GBA2 turns gentobiose prednisolone (Gbpdn) into an active drug.  Therefore, GbPdn exerted anti-inflammatory effects in wounded-tail zebrafish larvae and arthritis mice models and strongly reduced its side effects. We conclude that glycosylation of glucocorticoids turns these compounds into inactive prodrugs specifically targeted to inflamed tissue through local conversion by GBA2.