Diabetes mellitus is considered one of the major worldwide health emergencies of the twenty-first century. This work described development, synthesis, and characterization of new (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates. Compounds 7j and 7m were shown to be the most potent among the newly developed (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates after in vitro testing for α-glucosidase inhibitory activity. Following that, an in-vivo disaccharide loading test was performed on these compounds. From the cytotoxicity studies, the most potent substance (7m) was also founded non-toxic. To investigate the binding mechanism and important interactions of α-glucosidase's amino acid residues, docking analyses were completed and binding affinities of the synthesised compounds were observed from -7.1 to 9.6 kcal/mol. To determine the binding stability of the α-glucosidase protein with chemicals 7j and 7m, molecular dynamic simulations were employed. In silico research and prediction studies for absorption, distribution, metabolism, and excretion (ADME) were used to identify the "druggable" pharmacokinetic profiles. In this instance, we developed unique (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates as α-glucosidase inhibitors.