Snakebites affect ~1.8 million people annually. The current standard of care are antibody-based antivenoms, which are difficult to access and are not effective against local tissue injury, the primary cause of morbidity. Here we use a functional genomics approach to define human genes that genetically interact with spitting cobra venoms. From a whole genome CRISPR screen, we identified ~40 human genes that control venom outcomes. This list includes new receptors, signalling components, and epigenetic regulators, however across multiple venoms we found the top pathways hit all involved proteoglycan biosynthesis. Guided by this molecular insight, we targeted essential host / venom genes both genetically and pharmacologically, leading to a novel venom antidote that can specifically block the activity of three finger toxins. Critically, our new cobra venom antidote is safe and effective when delivered via its FDA dose and route. Overall, our systematic molecular dissection of cobra venom mechanisms provide new insight into how we can treat cobra bites, information that can help improve the lives of millions of people worldwide.