Converting dilute CO2 source into value-added chemicals and fuels is a promising route to reduce fossil fuel consumption and greenhouse gas emission, but integrating electrocatalysis with CO2 capture still faced marked challenges. Herein, we show that a self-healing metal–organic macrocycle functionalized as an electrochemical catalyst to selectively produce methane from flue gas and air with the lowest applied potential so far (0.06 V vs reversible hydrogen electrode, RHE) through an enzymatic activation fashion. The capsule emulates the enzyme’ pocket to abstract one in situ-formed CO2-adduct molecule with the commercial amino alcohols, forming an easy-to-reduce substrate-involving clathrate to combine the CO2 capture with electroreduction for a thorough CO2 reduction. We find that the self-healing system exhibited enzymatic kinetics for the first time with the Michaelis–Menten mechanism in the electrochemical reduction of CO2 and maintained a methane Faraday efficiency (FE) of 74.24% with a selectivity of over 99% for continuous operation over 200 h. A consecutive working lab at 50 mA·cm–2, in an eleven-for-one (10 h working and 1 h healing) electrolysis manner, gives a methane turnover number (TON) of more than 10,000 within 100 h. The integrated electrolysis with CO2 capture facilitates the thorough reduction of flue gas (ca. 13.0% of CO2) and first time of air (ca. 400 ppm of CO2 to 42.7 mL CH4 from 1.0 m3 air). The new self-healing strategy of molecular electrocatalyst with an enzymatic activation manner and anodic shifting of the applied potentials provided a departure from the existing electrochemical catalytic techniques.