Marine organisms have proven to be excellent sources of bioactive natural products with potential therapeutic applications. To date, seventeen marine-derived molecules are on the market for the treatment of human diseases, mainly cancer. While multiple bioactivities of marine compounds have been consecutively reported, peptides represent promising candidates for these applications. This review focuses on peptides from marine organisms living in extreme marine environments, such as the deep ocean, polar regions, and tropical ecosystems. These are particularly promising for further bioprospecting, since their distinctive conditions have driven the evolution of unique biomolecules, as well as unique stability profile that can improve efficacy, shelf life, and performance under a wide range of industrial conditions. Ziconotide (Prialt), a neurotoxic peptide derived from the venom of a marine snail (Conus sp.) found at depths greater than 1000 m, is already commercially available for the treatment of severe pain. Recent technologies and computational tools are speeding up the discovery of new peptides and enzymes (very few from extreme environments). Overall, the review reports about eight peptides with anticancer properties from deep environments, nine, two and seven from polar habitats with antioxidants, anti-inflammatory and anticancer properties, respectively, and approximately ninety peptides from tropical waters (five antioxidant, thirty-five anti-inflammatory and fifty-four anticancer peptides). However, future studies in extreme environments will need to develop and apply sampling technologies, cultivation systems, as well as methods to assess efficacy, side effects and mechanisms of action, in vitro and in vivo.