Peptide natural products play a significant role as a valuable source of bioactive agents for applications in medicine, agriculture, and biotechnology. These natural products can be classified into two categories: ribosomally synthesized post-translationally modified peptides (RiPPs) and nonribosomal peptides (NRPs). Within these classes, several RiPPs (such as lanthipeptides, lasso peptides, and amatoxins) and NRPs (including vancomycin, cyclosporine, and darobactin) have gained recognition due to their potent activities and unique structural features. Recent advances in genomic discovery have facilitated the rapid characterisation of a diverse range of new peptide natural products, often with elusive structures and unknown functions. However, their potential applications remain largely unexplored due to the limited quantities available for isolation. In this work, we aim to showcase our recent endeavors to chemically synthesize selected peptide natural products to access their distinctive architectures and investigate their functions.