The rising demand for aesthetic and comfortable orthodontic treatments has led to the widespread use of clear aligner therapy (CAT), a modern alternative to traditional braces. This umbrella review examines the biological effects of bisphenol A (BPA), a synthetic compound commonly found in clear aligner materials, focusing on its potential health risks. BPA is known for its estrogen-mimicking properties and has been associated with endocrine disruption and increased cancer risk. This review synthesizes findings from systematic reviews and meta-analyses to evaluate BPA leaching in aligner therapy and its implications for patient safety. A total of 25 studies were screened, with three high-quality systematic reviews included in the final analysis. In vitro studies generally reported minimal cytotoxicity and weak estrogenic effects, while clinical trials suggested higher BPA levels due to the dynamic oral environment. Risk of bias was assessed, and forest and funnel plots indicated consistent findings with low immediate toxicity but raised concerns regarding long-term hormonal effects. Given these findings, further research is recommended to assess BPA exposure under real oral conditions and to develop BPA-free aligner materials. This review underscores the importance of biocompatibility in orthodontic materials and the need for rigorous safety assessments to protect patient health.