Agri-food wastes are annually generated in huge amounts along the whole supply chain and are distinguished for their high moisture content, biological instability, organic load, and potential environmental impact, contributing to climate changes. For these reasons, agri-food waste reuse and recycle are highlighted by EU within a broader biorefinery concept. In this context, spent coffee grounds (SCGs) represent a promising source of high-added value compounds due to their appreciable amounts of polyphenols, caffeine, and lipids, which can be recovered to find applications in several industrial fields. Nevertheless, the unit operation of solid-liquid extraction, can be carried out by several alternative methods and solvents under different operating conditions. Green extraction processes can be seen as an alternative to conventional solvent extraction, but may entail new threats that require further investigation, since the equivalence between green and safer must not be taken for granted. Each option inevitably comprises several hazards, including fire and explosion to be “aprioristically” considered at the initial design stages. This work focuses on the implementation of specific inherent safety indexes to compare SCGs treatments alternatives for designing intrinsically safer plants and contributing to a more aware transition to green processes.