Schiff base compounds demonstrated exceptional efficiency and activity in the synthesis of several important drugs, including anti-tumor and anti-bacterial agents. Schiff base compounds proved their great efficiency and activity in the synthesis of some important drugs, such as anti-tumor, anti-bacterial, and anti-inflammatory agents. A new Schiff base (HEA) was synthesized from hydrocortisone and ethanol amine. The metal complexes were then formed. The metals selected for the preparation of complexes were derived from copper chloride, nickel chloride, magnesium sulfate, and vanadium sulfate. Fourier transform infrared (FTIR), nuclear magnetic resonance (1HNMR), mass, ultra-visible spectroscopy, and thermal studies were used to characterize the synthesized Schiff base ligand. While FTIR spectra, metal percent, UV-visible spectra, thermal analysis, magnetic measurements, and kinetic measurements were used to characterize the prepared complexes. We evaluated the application of biological docking using COX2 (PDB code: 5IKT (Homo sapiens)). The binding energy of HEA was -14.45 kcal/mol, slightly higher than hydrocortisone. The anti-inflammatory activity of hydrocortisone and HEA was tested in vitro and found to be selective for COX2 with IC50 values of 1.72 and 2.29, respectively.