Grey reef sharks are prey for larger sharks, such as the silvertip shark. At Rangiroa Atoll in French Polynesia, great hammerheads (Sphyrna mokarran) feed opportunistically on grey reef sharks that are exhausted from pursuing mates. Known parasites of this species include the nematode Huffmanela lata and several copepod species that attach to the sharks' skin, and juvenile stages of the isopods Gnathia trimaculata and G. grandilaris that attach to the gill filaments and septa (the dividers between each gill).
Although still abundant at Cocos Island and other relatively pristine sites, grey reef sharks are susceptible to localized depletion due to their slow reproductive rate, specific habitat requirements, and tendency to stay within a certain area. The IUCN has assessed the grey reef shark as Near Threatened; this shark is taken by multispecies fisheries in many parts of its range and used for various products such as shark fin soup and fishmeal. Another threat is the continuing degradation of coral reefs from human development. There is evidence of substantial declines in some populations. Anderson et al. (1998) reported, in the Chagos Archipelago, grey reef shark numbers in 1996 had fallen to 14% of 1970s levels. Robbins et al. (2006) found grey reef shark populations in Great Barrier Reef fishing zones had declined by 97% compared to no-entry zones (boats are not allowed). In addition, no-take zones (boats are allowed but fishing is prohibited) had the same levels of depletion as fishing zones, illustrating the severe effect of poaching. Projections suggested the shark population would fall to 0.1% of pre-exploitation levels within 20 years without additional conservation measures. One possible avenue for conservation is ecotourism, as grey reef sharks are suitable for shark-watching ventures, and profitable diving sites now enjoy protection in many countries, such as the Maldives.
Grey reef sharks are often curious about divers when they first enter the water and may approach quite closely, though they lose interest on repeat dives. They can become dangerous in the presence of food, and tend to be more aggressive if encountered in open water rather than on the reef. There have been several known attacks on spearfishers, possibly by mistake, when the shark struck at the speared fish close to the diver. This species will also attack if pursued or cornered, and divers should immediately retreat (slowly and always facing the shark) if it begins to perform a threat display. Photographing the display should not be attempted, as the flash from a camera is known to have incited at least one attack. Although of modest size, they are capable of inflicting significant damage: during one study of the threat display, a grey reef shark attacked the researchers' submersible multiple times, leaving tooth marks in the plastic windows and biting off one of the propellers. The shark consistently launched its attacks from a distance of 6 m (20 ft), which it was able to cover in a third of a second. As of 2008, the International Shark Attack File listed seven unprovoked and six provoked attacks (none of them fatal) attributable to this species.