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Glucagon-like peptide 2 (GLP-2) is a proglucagon-derived peptide released by intestinal endocrine cells. However, its therapeutic potential is limited by rapid inactivation via dipeptidyl peptidase-IV. The elucidation of three-dimensional structures of G-protein-coupled receptors, including GLP-2 receptor, has facilitated the rational design of novel peptide therapeutics. Recent studies have explored various structural modifications based on the structure of GLP-2, such as amino acid substitution, lipidation, and fusion with proteins, to extend the half-life of GLP-2 and enhance its biological activity. One promising avenue involves the development of multifunctional molecules targeting multiple pharmacological systems to boost therapeutic efficacy. This paper reviews the recent advancements in understanding GLP-2, including its physiological roles and structure-activity relationships, and evaluates the development prospects of GLP-2 analogs.