Abstract
Introduction: In the context of gingival conditions, certain medications can affect periodontal tissues by altering the inflammatory response and promoting gingival growth, resulting in gingival hyperplasia (GH) or gingival enlargement. Objective: It was to present the key clinical considerations regarding drug-induced gingival enlargement. Methods: The systematic review rules of the PRISMA Platform were followed. The search was conducted from March to April 2026 across the Web of Science, Scopus, Embase, PubMed, ScienceDirect, SciELO, and Google Scholar databases. A systematic review of the incidence of gingival hyperplasia and its relationship to the predictor phenytoin, nifedipine and cyclosporine A. The quality of the studies was assessed using the GRADE instrument, and the risk of bias was evaluated according to the Cochrane instrument. Results and Conclusion: According to the GRADE instrument, most studies presented homogeneous results, with X2=78.5% > 50%. A total of 83 articles were found and submitted for eligibility analysis, with 21 final studies selected to compose the results of this systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 33 studies with a high risk of bias and 13 studies that did not meet GRADE and AMSTAR-2 standards. It was concluded that drug-induced gingival overgrowth faces two therapeutic challenges: uncertain pathogenesis and a high recurrence rate. Analyzing the associations between medications and adverse reactions can help determine the treatment approach. Understanding the cytotoxicity thresholds of these medications is crucial for improving clinical outcomes and minimizing the incidence of gingival enlargement in patients requiring long-term therapy.