Two-dimensional transition metal dichalcogenides (TMDs) nanomaterials, such as MoS₂ and WSe₂, have proved to be promising electrocatalysts for CO₂ reduction, in which the reduction product is CO with high selectivity. In order to improve the sluggish CO desorption process and the overall electrocatalytic performance, we have extensively explored the optimal dopants in MoS₂ by high-throughput density functional theory (DFT) calculations and demonstrated the enhanced electrocatalytic activity. The dopants of V, Zr, and Hf into MoS₂ could significantly promote the desorption of CO from the MoS₂ edge, achieving the optimal performance for electrocatalytic CO₂ reduction. Furthermore, the dopants locating close to the active Mo site is crucial to influence the catalytic activity, while the dopant concentration is not important. The modulating strategy we proposed here also applies to other TMDs materials for enhancing electrocatalytic activity.