Abstarct: In this study, the causes of the difference in hydrogen bond strength and the chemical activity of dexamethasone(DX) and hydrocortisone(HD) compounds with Glucocorticoid¬ receptor (GR) were investigated by quantum calculations. For this purpose, structural and electronic parameters such as calculated molecular geometries, topological parameters of atoms in molecules (AIM) theory, natural bond orbital (NBO) analysis and UV-Vis spectra of the studied compounds are theoretically calculated. To determine the chemical activity of these compounds, frontier molecular orbital (FMO) analysis was performed along with calculation of general reactivity descxriptors. The local chemical properties at the B3LYP/6-311++G** level were also studied using molecular electrostatic potential (MEP) surfaces, average local ionization energy (ALIE). All calculations were performed using density functional theory (DFT) and time-dependent DFT (TD-DFT) at the B3LYP/6-311++G** level of theory. The results showed a good agreement between theoretical calculations and experimental data.