The species is endemic to the sandstone massif area of the western Arnhem Land region in the Northern Territory of Australia.

[6][7][8] Two notable characteristics of the species are the unusually large size of its eggs and its ability to change colour.

[11] In 1984, Wells and Wellington placed it into a new genus Nyctophilopython, and in 2014, a work by Reynolds, Niemiller, and Revell proposed to classify it as Simalia.

[15] As of September 2024, ITIS and the IUCN Red List identify the Simalia classification as valid,[16][17] while The Reptile Database uses Nyctophilopython.

[citation needed] The Oenpelli python occurs in a restricted range in the Northern Territory, in the sandstone outcrops of western Arnhem Land.

It is territorial, roaming between discrete positions, such as overhangs and caves in sandstone gorges or in a shady tree.

The conservation status of Nyctophilopython oenpelliensis is listed by the Northern Territory Government as vulnerable to extinction.

This has been evaluated by known threatening factors, such as altered land use and fire regimes, and population inferred from the relative abundance of its prey.

[18] One of the pythons in the program is featured at the Crocosaurus Cove herpetarium attraction in Darwin, Australia, which may be the only facility in the world that has a specimen on display for the general public.

[21] The Oenpelli python has historically been a totemic creature for the Bininj Aboriginal people and because of its iridescent scales it may also be associated with the Rainbow Serpent.