Today, the use of water-lean solvents in the absorption process to reduce greenhouse gas emissions has been contemplated by many researchers. To investigate the performance of the water-lean solvent, methyl diethanolamine-piperazine-methanol, in the absorption process of carbon dioxide in the microreactor, the effect of various factors such as: concentration of methyl diethanolamine-piperazine 30–50 wt%, temperature 20–40 °C, the solvent inlet flow 3–9 ml/min and the concentration of carbon dioxide 5–15 vol% were evaluated. The carbon dioxide removal percentage, volumetric mass transfer coefficient and molar flux have been considered as responses. The Box-Behnken Response Surface method was used to design the experiments and model the results. A quadratic model has been proposed to predict the responses. The order of the effect of the variables on the CO2 removal efficiency was as follows: solvent flow rate (49.55%) > solvent concentration (24.59%) > absorption temperature (18.05%). The highest CO2 removal efficiency of 94.62% was achieved at optimal temperature of 30 °C and CO2 concentration of 10 vol%, as well as the maximum concentration of amine and solvent flow. The results show that application of methanol as a low-cost and affordable physical solvent reasonably improves the carbon capture performance.