Methyltransferases (MTs) are a class of enzymes that are ubiquitous in biological organisms, usually using S-adenosylmethionine as a methyl donor to catalyze the methylation reaction of the substrate. The heterologous expression of MTs in microorganisms has made great progress in realizing the biosynthesis of some important natural products. MTs can be used in microorganisms to synthesize important natural products such as phenylpropanoids, fragrance compounds, hormones and antibiotics. MTs have also been widely used in many fields such as medicine, chemical industry and energy, showing great application value and broad application prospects. In this review, we summarize the classification, function and application of natural product methyltransferases, in order to provide theoretical guidance for the efficient artificial biosynthesis of highly active nonribosomal peptide synthetase (RXPs) peptides.