We report an effective and environmentally sustainable water treatment approach using enzymes encapsulated in biogenic vault nanoparticles. Manganese peroxidase (MnP), whose stability was remarkably extended by encapsulating into vaults, rapidly catalyzed the biotransformation of endocrine-disrupting compounds, including bisphenol A (BPA), bisphenol F (BPF), and bisphenol AP (BPAP). The vault-encapsulated MnP (vMnP) treatment removed 80-95% of each of the tested bisphenols (BPs) at lower enzyme dosage, while free native MnP (nMnP) only resulted in a 19-36% removal, over a 24-h period. Treatment by vMnP and nMnP resulted in considerable disparities in product species and abundance, which were consistent with the observed changes in the estrogenic activities of BPs. To test if vMnP-catalyzed transformations generated toxic intermediates, we assessed biological hallmarks of BP toxicity, namely, the ability to disrupt reproductive processes. The toxicity of vMnP-treated samples, as measured in the model organism, Caenorhabditis elegans, was dramatically reduced for all three BPs, including the reproductive indicators of BPA exposure such as reduced fertility and increased germ cell death. Collectively, our results indicate that the vMnP system represents an efficient and safe approach for the removal of BPs and promise the development of vault-encapsulated customized enzymes for treating other targeted organic compounds in contaminated waters.