<p>Peptide drugs are gaining increasing attention in biomedical research due to their unique advantages of customized sequence, high biosafety, exceptional selectivity and adjustable tissue accumulation. However, the widespread applications of peptide drugs are hindered by properties such as susceptibility to oxidation and hydrolysis, short half-life, and challenges in cellular membrane penetration. To promote the clinical application, modification strategies of peptides have been developed to enhance performance. In this review, the characteristics, development history, and wide applications of peptide drugs are systematically summarized, their advantages and limitations are highlighted, and the optimized performances of peptides are elucidated. Moreover, a detailed description of the modification methods for peptides is provided, encompassing both chemical and enzymatic modification strategies. The chemical modifications are divided into terminal modifications (C-terminus and N-terminus), cyclization, and residue modifications, and enzymatic modifications are categorized into natural enzymes and artificially modified enzymes. The advantages and limitations of these modification strategies are discussed in depth. In the end, the prospects of modified peptide drugs are proposed. This review provides a comprehensive overview of the current landscape of modified peptide drugs, which can benefit scientists in the interdisciplinary fields of chemistry, biomedicine, and pharmaceuticals.</p>