Electro-enzymatic conversion of CO₂ offers a promising solution for CO₂ utilization, while the conversion rate and efficiency were disappointing. To address the challenge, four kinds of natural deep eutectic solvents (NADES) with desirable biocompatibility were developed for the first time and used as the co-electrolyte in the electro-enzymatic conversion of CO₂. As a result, the SerGly-based solution presents high CO₂ solubility and high electrocatalytic activity, compared to the conventional buffer. By applying SerGly in the electro-enzymatic conversion of CO₂, the yield of the product (methanol) is two times higher than that in the Tris-HCl buffer (0.22 mM) and 16 times higher than the control reaction.