In the present study, a novel designed ultrasound-equipped microchannel reactor has been used to improve the CO2 desorption process from aqueous N-methyldiethanolamine (MDEA) solutions. CO2 desorption rate for a microreactor without ultrasound irradiation was compared with an ultrasound-equipped one at various temperatures, flow rates, and ultrasound powers. The results revealed that ultrasound vibrations could facilitate CO2 desorption and cause a significant increase in the rate of that through generation of cavitation bubbles and turbulence. Evaluation of energy and mass transfer characteristics was performed; 37.8% energy saving and 144.2% increase in mass transfer coefficient was obtained using ultrasound at its maximum power compared to microreactor without ultrasound irradiation. Also, comparisons between the designed sono-microreactor and conventional methods for CO2 desorption were performed in terms of desorption energy consumption and mass transfer coefficient, indicating 40.9% energy saving compared to 30 wt% MEA benchmark process and 160 times increase in mass transfer coefficient. Due to its high performance in terms of energy saving and mass transfer enhancement compared to the conventional method, the newly designed sono-microreactor can be introduced as a highly efficient technique for solvent regeneration.