The hydrogenation of glyoxylate oxime is the energy-intensive step in glycine electrosynthesis. To date, there has been a lack of rational guidance for catalyst design specific to this step, and the unique characteristics of the oxime molecule have often been overlooked. In this study, we initiate a theoretical framework to elucidate the fundamental mechanisms of glycine electrosynthesis across typical transition metals. By comprehensively analyzing the competitive reactions, proton-coupled electron transfer processes, and desorption steps, we identify the unique role of the glyoxylate oxime as a “readily activated molecule”. This inherent property positions Ag, featuring weak adsorption characteristics, as the “dream” catalyst for glycine electrosynthesis. Notably, a record-low onset potential of −0.09 V versus RHE and an impressive glycine production rate of 1327 µmol h⁻¹ are achieved when using an ultralight Ag foam electrode. This process enables gram-scale glycine production within 20 h and can be widely adapted for synthesizing diverse amino acids. Our findings underscore the vital significance of considering the inherent characteristics of reaction intermediates in catalyst design.