Abstract: A method for synthesizing peptide thioesters and a head-to-tail amide cyclic peptide thereof, which belongs to the technical field of chemical pharmaceuticals and fine chemical preparation. The method comprises the following steps: (1) using resin A as a carrier and using a solid-phase synthesis strategy to obtain a resin peptide; (2) cutting the resin to obtain a fully protected peptide; (3) performing an esterification reaction with p-chlorophenyl thiophenol in a TCFH/alkali condensation system to generate p-chlorophenyl thioester; (4) removing the protecting group to obtain a peptide thioester; and (5) further cyclizing to obtain a head-to-tail cyclic peptide. The preparation of the thioester peptide and the head-to-tail amide cyclic peptide provides a simple technical route with wide universality and a high yield, and has a wide range of applications in the technology of chemical pharmaceuticals and fine chemical preparation.