Aim: The objective of this study was to investigate the therapeutic potential of quercetin (QT) and QT-loaded poly(lactic-co-glycolic acid) nanoparticles (QT-NPs) on Cerastes cerastes venom-mediated inflammation, redox imbalance, hepatorenal tissue damage and local hemorrhage. Methods: The developed QT-NPs were first submitted to physicochemical characterization and then evaluated in the ‘challenge then treat’ and ‘preincubation’ models of envenoming. Results: QT-NPs efficiently alleviated hepatorenal toxicity, inflammation and redox imbalance and significantly attenuated venom-induced local hemorrhage. Interestingly, QT-NPs were significantly more efficient than free QT at 24 h post-envenoming, pointing to the efficacy of this drug-delivery system. Conclusion: These findings highlight the therapeutic potential of QT-NPs on venom-induced toxicity and open up the avenue for their use in the management of snakebite envenoming.