<p>Titanium alloy anastomotic staples are widely used in gastrointestinal surgery due to their ability to reduce operative time and standardize anastomotic construction. The developmental focus of these devices has evolved from ensuring basic mechanical reliability toward improving biocompatibility and, more recently, toward functionally engineering the staple–tissue interface to actively regulate healing outcomes. Current research efforts primarily target three interrelated challenges: enhancing tissue integration, preventing bacteria-associated anastomotic complications, and enabling controlled biodegradability, particularly in the context of malignant gastrointestinal disease. To address these challenges, a range of material modification strategies—including surface coatings, biochemical functionalization, physical micro/nano-topographical engineering, and biodegradable metal design—have been explored. In this review, we systematically survey studies published since 2010, identified through searches of major biomedical and materials science databases, with emphasis on experimental models directly relevant to gastrointestinal anastomosis. Rather than providing a descriptive catalog, this review critically analyzes how distinct modification strategies influence cellular responses, inflammatory regulation, and translational feasibility within the unique anastomotic microenvironment. Despite increasing research activity, an integrative framework linking mechanistic insights to clinical performance remains insufficiently developed. By synthesizing current evidence and highlighting unresolved biological and translational challenges, this review aims to clarify the functional design principles of next-generation anastomotic staples and to inform future development of clinically viable, bioactive surgical implants.</p>