Bisphenol (BP) compounds are widely present in the environment, primarily due to their use as plastic additives. These substances involve health risks, particularly as endocrine disruptors. While the general population is chronically exposed, patients with end-stage chronic kidney disease undergoing hemodialysis (HD-CKD) represent a particularly vulnerable group. This is due to both impaired renal clearance of circulating BPs and potential contamination from plastic-containing dialyzers used in extracorporeal blood circulation. In this longitudinal study, from the 35 HD-CKD patients initially selected, 25 changed their conventional dialyzers to BPA-free dialyzers for 6 months. Blood serum samples were collected, at baseline and after the intervention, to quantify levels of five BP analogues: Bisphenol A (BPA), Bisphenol AF (BPAF), Bisphenol F (BPF), Bisphenol B (BPB), and Bisphenol S (BPS). Genotoxicity was assessed using the comet assay and the micronucleus test on peripheral white blood cells. Among the analyzed BPs, only BPAF showed a statistically significant reduction when using BPA-free dialyzers. In terms of genotoxicity, a significant decrease was observed only in primary DNA damage (mainly DNA strand breaks), with no notable changes in chromosomal damage. This is the first study to detect multiple BP analogues in HD-CKD patients, beyond BPA, and to associate human exposure to BPs with DNA damage biomarkers. The observed reduction in DNA damage in parallel with decreased BPAF levels highlights the importance of monitoring and minimizing BP exposure of this high-risk population.