Protective and Healing Effects of Zinc L-Carnosine on the Oral Mucosa: A Systematic Review and Meta-Analysis.

Background/Objectives: Oral mucosal injury is a frequent complication in oncologic and surgical settings, significantly affecting patient quality of life. Zinc L-carnosine (ZnC) is a cytoprotective compound with anti-inflammatory, antioxidant, and epithelial reparative properties. This systematic review evaluated its protective and healing effects on oral mucosa. Methods: A systematic search followed PRISMA guidelines was conducted across PubMed, Scopus, Web of Science, and Cochrane Library (2015-2026). Randomized and non-randomized controlled studies assessing ZnC in patients with or at risk of oral mucosal injury were included. Risk of bias was evaluated using RoB 2 and ROBINS-I tools. Meta-analyses were conducted under both common- and random-effects models. The certainty of evidence was evaluated according to the GRADE guidelines. Results: Eight studies (n = 544) were included. Six non-randomized studies showed moderate or serious risk of bias, while randomized trials presented some concerns. ZnC was administered in different formulations, including mouthwashes, lozenges, and mucoadhesive suspensions based on sodium alginate, polyacrylic acid, and carboxyvinyl polymer, and across different clinical settings. Meta-analysis showed a reduced incidence of severe oral mucositis (grade ≥ 3) under the Common Effect model (OR 0.48; 95% CI 0.32-0.72), although statistical significance was not maintained under random-effects models (OR 0.44; 95% CI 0.18-1.06). Similar results were observed for grade ≥ 2 mucositis. According to the GRADE assessment, the certainty of evidence was low for oral mucositis outcomes and very low for oral mucosal healing. Only one study suggested improved surgical wound healing. No serious adverse events were reported. Conclusions: ZnC may support oral mucosal protection and healing, particularly in preventing oral mucositis. However, substantial heterogeneity and limited high-quality randomized evidence restrict the strength of conclusions. Further well-designed randomized trials are needed.