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These tumors have a high incidence, are often asymptomatic, and are prone to metastasis and recurrence, posing a significant public health burden. Although traditional methods such as radiotherapy and chemotherapy can delay disease progression, their nonspecific effects often lead to severe side effects and drug resistance, resulting in limited efficacy. Therefore, developing novel treatment strategies with high target specificity and favorable biological safety is a critical scientific issue in this field. Peptide drugs offer advantages such as good biocompatibility, low immunogenicity, diverse structures, and ease of modification, collectively demonstrating unique potential for tumor treatment. They can not only achieve precise delivery by specifically recognizing tumor receptors but can also directly interfere with signal transduction, metabolism, and immune regulation, producing multi-target antitumor effects. This article systematically reviews the research progress of peptide drugs in gastrointestinal tumors, focusing on their molecular mechanisms, delivery modification strategies, and the latest applications. It also summarizes the challenges and future directions for clinical translation, providing a theoretical foundation and future perspectives for the precise treatment of gastrointestinal tumors and the design of new drugs.<\/jats:p>","DOI":"10.3390\/biom16030456","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:35:08Z","timestamp":1773819308000},"page":"456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peptide Drugs in Gastrointestinal Tumors: Integrating Targeting, Delivery, and Therapeutic Actions for Synergistic Strategies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0036-0879","authenticated-orcid":false,"given":"Qian","family":"Ouyang","sequence":"first","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, 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