This study presents a novel, metal-free, acid- and base-free electrochemical method for the C4-selective deuteration of pyridine derivatives using economic and convenient D₂O at room temperature. The approach features high chemo- and regioselectivity, enabling the synthesis of a wide range of D-compounds, including pyridines, quinolones, N-ligands, and biorelevant compounds. Mechanistic studies and cyclic voltammetry (CV) experiments reveal that N-butyl-2-phenylpyridinium iodide is a crucial intermediate in the electrochemical transformation, offering a general and efficient way for deuteration of pyridine derivatives. Deuterium-labeled molecules are critical in various research areas, including reaction mechanism studies, isotopic tracer techniques, and pharmaceutical chemistry. Pyridine derivatives, commonly used as bioactive molecules and drugs, have attracted significant attention for their applications in pharmacokinetic and pharmacodynamic studies. Despite existing methods for deuteration, challenges remain in achieving high selectivity under mild conditions. The current study addresses these challenges by developing an efficient, sustainable, and direct electrochemical C–H deuteration strategy. The method involves the electrochemical reduction of pyridine derivatives in an undivided cell with graphite felt as the anode and lead plate as the cathode, using D₂O as the deuterium source. The optimal conditions were determined through systematic screening, leading to high yields and deuterium incorporation. The method was tested on a wide range of substrates, including various substituted pyridines, quinolines, N-ligands, and biorelevant compounds, demonstrating excellent selectivity and efficiency. Mechanistic studies, including CV experiments, revealed that N-butyl-2-phenylpyridinium iodide plays a key role in the reaction, facilitating the electrochemical deuteration process. The method was also tested at a gram-scale and in a continuous-flow setup, showing its potential for industrial applications. The results indicate that this electrochemical approach offers a promising and sustainable method for the deuteration of pyridine derivatives and other compounds.This study presents a novel, metal-free, acid- and base-free electrochemical method for the C4-selective deuteration of pyridine derivatives using economic and convenient D₂O at room temperature. The approach features high chemo- and regioselectivity, enabling the synthesis of a wide range of D-compounds, including pyridines, quinolones, N-ligands, and biorelevant compounds. Mechanistic studies and cyclic voltammetry (CV) experiments reveal that N-butyl-2-phenylpyridinium iodide is a crucial intermediate in the electrochemical transformation, offering a general and efficient way for deuteration of pyridine derivatives. Deuterium-labeled molecules are critical in various research areas, including reaction mechanism studies, isotopic tracer techniques, and pharmaceutical chemistry. Pyridine derivatives, commonly used as bioactive molecules and drugs, have attracted significant attention for their applications in pharmacokinetic and pharmacodynamic studies. Despite existing methods for deuteration, challenges remain in achieving high selectivity under mild conditions. The current study addresses these challenges by developing an efficient, sustainable, and direct electrochemical C–H deuteration strategy. The method involves the electrochemical reduction of pyridine derivatives in an undivided cell with graphite felt as the anode and lead plate as the cathode, using D₂O as the deuterium source. The optimal conditions were determined through systematic screening, leading to high yields and deuterium incorporation. The method was tested on a wide range of substrates, including various substituted pyridines, quinolines, N-ligands, and biorelevant compounds, demonstrating excellent selectivity and efficiency. Mechanistic studies, including CV experiments, revealed that N-butyl-2-phenylpyridinium iodide plays a key role in the reaction, facilitating the electrochemical deuteration process. The method was also tested at a gram-scale and in a continuous-flow setup, showing its potential for industrial applications. The results indicate that this electrochemical approach offers a promising and sustainable method for the deuteration of pyridine derivatives and other compounds.