The invention belongs to the technical field of pharmaceutical chemistry, and discloses a preparation method of semaglutide and an intermediate of semaglutide. The preparation method comprises: obtaining a compound having a structure represented as the formula I by taking a resin, activating the resin, and coupling L-glycine, L-arginine, L-glycine, L-arginine, L-valine, L- leucine, L-tryptophan, L-alanine, L-isoleucine, L-phenylalanine, and L-glutamic acid to the activated resin step by step so as to obtain a first peptide resin; taking the first peptide resin, and coupling amino acids or amino acid derivatives to the second peptide resin step by step; and taking the second peptide resin, and performing cracking and purifying to obtain semaglutide. According to the method, the compound having a structure represented as the formula I is taken as an intermediate and coupling of each amino acid or amino acid derivative step by step through solid-phase synthesis is carried out, thereby improving the yield of semaglutide. In the formula I, R1 is selected from Fmoc, Boc, and ivDde, and R2 is selected from tBu, Dmab, and Bzl.