Abstract: The development of mass spectrometry and proteomics significantly advanced our understanding of post-translational methylation of proteins. In recent years, a large number of proteins containing the methylation recognition domain have been identified. Protein methylation mainly occurs on lysine and arginine residues. Both lysine and arginine have three different methylation states. Lysine can be mono-methylated, di-methylated, and tri-methylated, while the arginine residue can be modified as mono-methylation, symmetrical di-methylation, and asymmetrical di-methylation. Methylation recognition domains can accurately identify lysine or arginine with different state of methylation, transfer methylation signals, and perform functions in a variety of cellular processes, including gene expression regulation, RNA splicing and translation, cell cycle regulation, etc. In recent years, researchers have found that the abnormalities of these recognition proteins are also closely related to the genesis and development of tumors. Therefore, these methylation recognition proteins were considered as potential drug targets for small molecule intervention. In this review, we summarized the researches on the recognition domains of protein methylation as well as their inhibitors, hoping to provide the basis for further drug development in this field.