Abstract: Exogenous glucocorticoids (GCs) are widely used in clinical treatment of inflammatory diseases, with their mechanism of action mainly through glucocorticoid receptor (GR). However, the use of GCs is limited by the adverse reactions caused by their longterm and large-scale application. The academic community is making continuous efforts to find safer GR regulators. This article introduces the mechanism of GR and the adverse reactions caused by long-term use of GCs, and summarizes the research progress of new safer GR modulators in recent years, in order to provide some reference for the development of new GR ligands.