Background: A substantial number of thiazolidin-4-one derivatives have been shown to have a variety of pharmaco­logical characteristics.Aim: The current study seeks to design new acetazolamide products with thiazolidin-4-one moiety and evaluate their inhibitory effect to carbonic anhydrase XII enzyme (protein data bank code: 1JD0) and anti-cancer properties in silico. Four acetazolamide derivatives with a thiazolidin-4-one moiety will be produced using acetazolamide as the starting material.Methodology: The molecular docking studies were determined by utilizing the Molecular Operating Environment (MOE) software version 2015.10. The binding tendencies of docked ligands to the target protein carbonic anhydrase XII were described as root-mean-square deviation (RMSD) and standard score (S score).Results: The process of docking demonstrated that the four test ligands (IIIa, IIIb, IIIc, and IIId) had a higher binding affinity for the objective protein carbonic anhydrase XII than the reference ligand, which is an acetazolamide. Consid­ering the four compounds, the compound IIIa had the ultimate affinity of binding, and S score of -7.4.Conclusion: The findings imply that the designed acetazolamide compounds, specifically IIIa, have the potential to be carbonic anhydrase inhibitors and anti-cancer medicines that target the carbonic anhydrase XII enzyme.