Per and polyfluoroalkyl substances (PFAS) in drinking water sources exceed European Food Safety Authority (EFSA) concentration limits, and are linked to immune suppression, thyroid disease, and cancer. Adsorption effectively removes PFAS, but Granular Activated Carbon (GAC) faces limitations with high energy consumption and mass losses in its reactivation and short-chain PFAS removal. Innovative adsorbent materials have been developed, but their selection and regeneration for drinking water applications remain unresolved. Here we evaluate a high-silica (BEA) zeolite and a crosslinked beta-cyclodextrin polymer (DEXSORB+) for PFAS adsorption and chemical regeneration via batch experiments using drinking water spiked with PFAS concentrations of 110 ug/L as sum of 11 PFAS. We conducted five adsorption-regeneration cycles using ethanol- and acetic acid-based regenerants, alongside a Life Cycle Assessment (LCA) comparing the health and environmental impacts of the novel adsorbents to GAC. LC-MS analysis confirms both adsorbents provide > 75% removal and > 75% regeneration efficacy after 5 cycles for the ethanol-based treatment. The acetic acid failed to regenerate the zeolite (3% regeneration efficacy) despite > 99% PFAS removal. However, pre-conditioning of DEXSORB+ is needed to mitigate leaching organics into the treated water (dissolved organic carbon, UV absorbance). LCA reveals that regeneration solution dosage optimization is critical to outperform GAC’s thermal reactivation, as solution production and waste handling contribute to > 90% of disability-adjusted life years (DALYs). Due to the production, handling, and disposal of ethanol, regeneration imposes 7 times higher DALYs than GAC reactivation.