AbstractAntivirulence therapy has proven to be an attractive method for the treatment of bacterial infections and venomous injuries; however, the approaches for neutralizing multiple types of virulence through one platform are limited. To address this challenge, we have developed a reactive conjugated polymer, PPV–NHS, which functions as a broad-spectrum antidote for directly inactivating basic toxins. The antivirulence is achieved via multivalent electrostatic recognition and subsequent amidation reactions between PPV–NHS and toxins. The resultant bioconjugates significantly reduced neurotoxicity and cytotoxicity. In the mouse model, PPV–NHS effectively inhibited the toxicity of cardiotoxin (CTX) and improved the survival rate of toxin-challenged mice. This work represents the rational design of functionalized conjugated polymers for antivirulence therapy with both high efficiency and broad applicability.