This review investigates whether materials used in removable orthodontic retainers exhibit toxic effects on cells or interfere with hormonal balance. Publications from 2015–2025 were evaluated. The scope included in vitro studies on cellular toxicity and estrogenic response, in vivo tissue observations, and clinical markers in retainers fabricated from PMMA plates, thermoplastic foils, photopolymerized 3D resins, PEEK, and fiber-reinforced systems. Screening of electronic databases yielded 38 laboratory studies and 10 clinical reports. Among tested substances, photopolymer-based resins showed the strongest adverse effects on cells, whereas PMMA and thermoplastic sheets typically demonstrated only minor impacts, which diminished after immersion in water for 24 hours. Leaching of bisphenol derivatives was detected; however, systemic absorption remained within accepted safety thresholds. Clinical evidence did not reveal significant oral tissue alterations or hormone-related outcomes. Most materials employed for retainers appear biocompatible, although evidence concerning prolonged endocrine effects is still insufficient. Harmonized methods for safety evaluation are required to compare across different appliance types. Additionally, disposable thermoplastics generate microplastic particles and complicate waste handling, presenting environmental concerns.
