<p>Diabetes Mellitus (DM) is a chronic and multifactorial health issue affecting a large portion of the worldwide population. Type 2 DM is the utmost prevalent form of diabetes, representing approximately 90–95% of all diabetes cases. The researchers have revealed a great interest in identifying effective and safe inhibitors of <i>α</i>-amylase and <i>α</i>-glucosidase to manage T2DM. In search of potent antidiabetic agents, quinoxaline has been proven as a significant core structure in medicinal chemistry. Therefore, a highly efficient one-pot synthesis of sixteen quinoxalines has been developed using theophylline hydrogen sulfate as a solid acid catalyst. The synthesis of quinoxaline was accomplished by performing a cyclo-condensation reaction at room temperature between different 1,2-diketones/ ninhydrin and substituted <i>o</i>-phenylenediamine using EtOH + H₂O (1:1) solvent. ¹H NMR, ¹³C NMR and mass spectra were used to analyze the synthesized derivatives. The present study employed mild reaction conditions, didn’t require chromatographic separation, a short reaction time (5–30&#xa0;min), and demonstrated excellent yields (91–98%), selectivity, efficiency, and an easily recovered catalyst that is highly reusable up to six cycles. Several green metrics were used to evaluate the protocol’s greenness. Moreover, the sixteen synthesized quinoxalines were docked within the binding site of the selected PDBs 4GQR and 5NN6 to identify them as potent antidiabetic agents.</p> Graphical abstract <p></p>