Its status in many Aboriginal cultures is evident in the totemic relationships, and part of the Ngiṉṯaka dreaming, as well as bush tucker.

British zoologist John Edward Gray described the perentie in 1845 as Hydrosaurus giganteus, calling it the "gigantic water lizard".

Previously, bites inflicted by monitors were thought to be prone to infection because of bacteria in their mouths, but the researchers showed that the immediate effects are caused by mild envenomation.

[10] University of Washington biologist Kenneth V. Kardong and toxicologists Scott A. Weinstein and Tamara L. Smith have argued that the suggestion of venom glands "... has had the effect of underestimating the variety of complex roles played by oral secretions in the biology of reptiles, produced a very narrow view of oral secretions and resulted in misinterpretation of reptilian evolution".

Typical of most goannas, the perentie either freezes (lying flat on the ground, and remaining very still until the danger has passed) or runs if detected.

If cornered, this powerful carnivore stands its ground and uses its arsenal of claws, teeth, and whip-like tail to defend itself.

[12] They are highly active carnivores that feed on mostly reptiles, small mammals, and less commonly birds such as diamond doves.

Coastal and island individuals often eat a large number of sea turtle eggs and hatchlings and hide under vehicles to ambush scavenging gulls.

[18] Although adults feed predominantly on vertebrate prey, young perenties eat mostly arthropods, especially grasshoppers and centipedes.