The goal of this investigation is the action mechanism study of bergenin and acetylated derivative as non-steroidal anti-inflammatory drugs (NSAIDs) using quantum chemistry calculations at the B3LYP level of theory, together with the 6-31G* basis set. The anti-inflammatory potencies of the drug candidates were correlated with electronic, steric, and solubility parameters. Furthermore, molecular charge is a parameter of reactivity with Ser-580 on the active site of the prostaglandin-endoperoxide sinthase (PGES) that was explored, showing a preferential reaction with one phenolic esther.