Initial geometry optimizations for all of the compounds were carried out using the molecular mechanics (MM) approach and the MM+ force fields in this study, which investigated QSAR on several bioactive sulfonamide compounds. The Density Functional Theory (DFT) method using Becke's three-parameter hybrid functional (B3LYP) and 6-31G (d) basis set enhanced the lowest energy conformations of the compounds generated by the MM method. The following parameters calculated from DFT calculations, such as molecular descriptors, dipole moment, electro negativity, total energy at 0 K, entropy at 298 K, HOMO and LUMO energies, provide important information and play a major role in the estimation of carbonic anhydrase (CA-II) inhibitory activity of the compounds. Several QSAR models were created using the multiple linear regression technique to calculate descriptors and carbonic anhydrase (CA-II) inhibitory data of the compounds. The statistically most significant of the above-mentioned QSAR models is a five-parameter linear equation with squared correlation coefficient R2 values of about 0.7629 and adjusted correlation coefficient R2A values of around 0.6612. The carbonic anhydrase (CA-II) inhibitory activity was investigated in the context of regulatory variables. Computer-aided drug design is looking forward to a bright future thanks to Molecular Dynamic Simulation techniques for exploring the therapeutic potential of medicinal medicines and antibodies. Molecular dynamic stimulation can help to extend the work that has already been done.