Introduction 5-Fluorouracil (5-FU) is an adjunct therapeutic agent in facial plastic surgery, treating hypertrophic scars, keloids, granulomas, contractures, and thickened nasal skin. It reduces scars, enhances aesthetics, and improves function with a favorable safety profile. This systematic review evaluates the evidence for 5-FU use in facial aesthetics. Methods Comprehensive searches in MEDLINE, Cochrane, SCOPUS, EMBASE, PubMed, and Web of Science identified studies on 5-FU in facial aesthetics. Results From 4,772 articles, 32 studies (1,456 patients) met criteria. Indications included keloids, hypertrophic scars, and contractures (18 studies)
periocular scars (6)
granulomas (4)
nasal skin thickening (1)
infections (1)
resistant warts (1)
and hypochromic lesions (1). Most studies reported improvements in scar dimensions and erythema. Combination therapies and innovative delivery methods enhanced outcomes with minimal side effects. Conclusion Findings support 5-FU as a safe, minimally invasive therapy, achieving aesthetic and functional goals. However, standardized protocols and long-term studies are needed.