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Lead (Pb(II)) is a pervasive heavy metal toxin with many well-established negative effects on human health. Lead toxicity arises from cumulative, repeated environmental exposures. Thus, prophylactic strategies to protect against the bioaccumulation of lead could reduce lead-associated human pathologies. Here we show that DNA and RNA aptamers protect C. elegans from toxic phenotypes caused by lead. Reproductive toxicity, as measured by brood size assays, is prevented by co-feeding of animals with DNA or RNA aptamers. Similarly, lead-induced neurotoxicity, measured by behavioral assays, are also normalized by aptamer feeding. Further, cultured human HEK293 and primary murine osteoblasts are protected from lead toxicity by transfection with DNA aptamers. The osteogenic development, which is decreased by lead exposure, is maintained by prior transfection of lead-binding DNA aptamers. Aptamers may be an effective strategy for the protection of human health in the face of increasing environmental toxicants., Competing Interests: Declaration of Competing Interest N.G.F., A.A., and S. Ramis de Ayreflor Reyes have filed a patent application for the technology described herein. J.H.S. is a scientific co-founder of AAVAA Therapeutics and holds equity in this company. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)