ENSURESEC is a sociotechnical solution for safeguarding the Digital Single Market’s e-commerce operations against cyber and physical threats. It combines an automatic, rigorous, distributed and open-source toolkit for protecting e-commerce, with monitoring of the impact of threats in physical space and a campaign for training SMEs and citizens aimed at creating awareness and trust. ENSURESEC addresses the whole gamut of modern e-commerce, from standard physical products purchased online and delivered via post, to entirely virtual products or services delivered online. It addresses threats ranging from maliciously modifying web e-commerce applications or rendering them unavailable to legitimate customers, to delivery issues or fraud committed by insiders or customers. It achieves this by focusing on the common software and physical sensor interfaces that sit along the e-commerce, payment and delivery ecosystem. At technical level, it integrates proven state-of-the-art inductive (machine learning) with deductive (formal methods) reasoning tools and techniques so that e-commerce operations are protected by design, as well as through continuous monitoring, response, recovery and mitigation measures at run-time. Importantly, trust of the infrastructure’s operations among its users is established, benefiting from distributed ledger technology ensuring transparency of the operations and that information has not been modified. Although ENSURESEC innovations are applicable to any critical infrastructure that relies and is monitored by networked software systems, its design and integration philosophy make it uniquely prepared to protect distributed and evolving e-commerce infrastructures with its various forms of payment and delivery (virtual, online and physical). ENSURESEC also enhances citizens’ resilience to threats and their trust in e-commerce companies, especially SMEs, thus contributing towards the vision of a reliable and trusted digital single market.