Once three beautiful siblings among the Old Gods. During the fall of Agharta, the three sisters escaped into the deep depths of the earth. They became twisted shadows of their former selves, while retaining the macabre appearances of little girls. Over the many years they have survived by obsessively staying together. Their lair would become part of the City of the Damned under the castle, where they would become loyal followers of their new Prince of Darkness.
Dracula learns from young Trevor that the Gorgons possess his Chaos Claws. Upon finding Euryale, she tells him that the jailers have turned against him. Stheno informs Dracula that Medusa has the claws. Dracula enters the Gorgon's lair, and among the endless petrified victims he retrieves his power. The three sisters unite, only to learn that Medusa has been corrupted by the Castle's blood and infects her sisters as well. The blood takes them in and combines them into a singular mighty Gorgon that battles Dracula.
- Medusa is a classic enemy in past installments. Her Lords of Shadow incarnation has a more "European influence" along with the usual Greek inspiration, as stated by David Cox.
- While Medusa has appeared in many Castlevania games, Lords of Shadow 2 is the first to feature Stheno and Euryale.
- As with Medusa, Stheno and Euryale are both Gorgons from classical Greek myth, and the elder sisters of the famous mythological monster. Medusa is always depicted as being a beautiful mortal prior to becoming a gorgon, but her sisters were born immortal and, depending on the given story, either were born as hideous gorgons or were also once young women. In the latter scenario, when Medusa was punished by Athena for the defilement of the goddess's temple, Stheno and Euryale tried to defend Medusa from Athena's wrath. Angered, the goddess changed the remaining sisters into gorgons as well, but it is not known if they also had Medusa's ability to petrify the living with a glance. However, all three sisters were shown to be highly lethal after their transformations, so much so that the hero Perseus, in order to slay Medusa, was forced to enter their lair while the sisters were sleeping, to avoid detection and retaliation from the gorgons.
- In keeping with their Greek inspiration, while not having snakes for hair, the Gorgon Sisters have snakelike appendages protruding and encircling parts of their bodies. The sound of a rattlesnake's warning rattle can also be heard when any sister appears. Furthermore, their bodies contort easily, perhaps in a dark homage to the flexibility of real snakes.
- Medusa's power of petrification does not appear to work on creatures which are not human, although it is possible that she might be able to use her power at will rather than it working on a living creature automatically. The latter theory is supported by the boss fight between Gabriel and the merged Gorgons.
- The Gorgon sisters' appearances are inspired by horror film creatures similar to The Ring and The Grudge, particularly in the disturbing way they move, accompanied by the usage of audio and camera effects notable on these two horror films.
- They share loose similarities to the witches, being three witch-like individuals living deep under the castle, and both end up more or less turning on their master (although the witches intentionally plotted for dominance of the castle). The witches might have also been loosely inspired by the Graeae sisters, three witches who were relatives to the mythic Gorgons.
- In Revelations, a statue of the Gorgon Sisters is found in the main chamber of the Forbidden Wing. This shows a kind of reverse foreshadowing; Alucard first finds the Chaos Claws being held by this statue, hinting that the relic would eventually end up in Medusa's possession. The blood that later floods the chamber is another foreshadowing to the ultimate fate of the Gorgon Sisters.
- The Gorgon Sister may also be an alternate depiction of the "Weird Sisters", also known as the "Brides of Dracula", featured in Bram Stoker's 1897 novel Dracula. However, since in the game they don't seem to have any kind of intimate relationship with Dracula, as shown in other media, it's unclear how they serve him exactly.