Depredation is defined as the damage or removal of fish from fishing gear by predators, and is a crucial issue leading to negative impacts on both animals involved in depredation and fisheries. Depredation in longline pelagic fisheries targeting swordfish (Xiphias gladius) and tuna (Thunnus spp.) involves short-finned pilot whales (Globicephala macrorhynchus), false killer whales (Pseudorca crassidens) and some pelagic sharks. Since no long-term solution could be found to date, we investigated fishing gear improvement by deploying a technology designed to physically protect the hooked fish by hiding it to predators: the DMD (depredation mitigation device). Two types of DMDs were designed: “spiders” and “socks”. The efficiency of “spiders” was tested in November 2007 during a fishing trial of 26 longline fishing operations when 12,480 hooks and 1970 devices were set. The efficiency of “socks” was tested in October 2008 during a fishing trial of 32 longline fishing operations when 13,220 hooks and 339 devices were set. 117 and 24 fish were hooked on branchlines equipped with spiders and socks, respectively and among those devices, 87.3% versus 69.2% were correctly triggered and 80% versus 15% of the fish were correctly protected. A low entanglement rate of the spiders with the fishing gear was found (3.6%), but a higher one was associated to the socks (17.8%). Operational constraints to routinely deploy “spiders” were examined. The number of sets impacted by shark depredation was significantly greater than the number of sets involving toothed whale depredation. However, when depredation occurred, the proportion of fish damaged by toothed whales was significantly greater. While more trials should be carried out to deeply verify the efficiency of DMDs, we remain convinced that considerations of fishing gear technologies might be more actively investigated to propose innovative measures to mitigate toothed whale depredation in pelagic longlining. For this type of gear, innovative technology is an important issue of the ecosystem approach to fisheries (EAF) framework.