To investigate the potential cytotoxic and hormone-disrupting effects of materials commonly employed in removable orthodontic retainers. Studies published between 2015 and 2025 were reviewed, including in vitro assessments of cell toxicity, estrogenic activity, in vivo tissue responses, and clinical biomarker evaluations of PMMA plates, thermoplastic foils, 3D-printed resins, PEEK, and fiber-reinforced composites. A total of 38 laboratory studies and 10 clinical studies satisfied the inclusion criteria. Photopolymer-based resins showed the greatest cytotoxicity, whereas PMMA and thermoplastics induced mostly mild effects that further decreased after 24 hours of water immersion. Release of bisphenol-related compounds was observed, but systemic levels remained below safety limits. Clinical observations did not reveal significant mucosal changes or endocrine-related outcomes. Overall, removable retainer materials exhibit satisfactory biocompatibility, though evidence regarding long-term endocrine effects is scarce. Standardized testing protocols are needed to enable reliable comparisons across material types. Furthermore, the use of disposable thermoplastics raises microplastic pollution concerns and complicates waste management, highlighting sustainability issues.
