Protein lysine monomethylation is an important post-translational modification participated in regulating many biological processes thus there is growing interest in identifying these methylation events. However, the introduction of one methyl group on lysine residues has negligible effect on changing the physical and chemical properties of proteins or peptides, making enriching and identifying monomethylated lysine (Kme1) proteins or peptides extraordinarily challenging. In this study, we developed an antibody-free chemical proteomics approach to effectively capture Kme1 peptides, involving reductive glutaraldehydation of peptides and hydrazide chemistry. By optimizing the reaction condition of reductive glutaraldehydation, aldehyde modified Kme1 residues and piperidine modified primary amines were generated at the same time so that solid-phase hydrazide chemistry could be applied to effectively capture Kme1 peptides from complex mixture. Using this chemical approach, we can enrich and detect Kme1 peptide from peptide mixture containing 5000-fold bovine serum albumin tryptic digest.