The game takes place in its own continuity, where the player assumes the role of a new female student at Monster High. This student can be customized by combining a number of premade trait options, such as facial design, skin color, and outfit. The goal of the game is to befriend the other students and earn the respect of the teachers to eventually become the Scream Queen at the Terror Under The Sea dance.
All three versions of Ghoul Spirit are the exact same game, though with accommodations made in response to the abilities and limitations of the platforms. The DS and DSi versions are identical, but the DSi version allows the player to take a photo of themself and use it to customize the avatar around.
The Wii version does not allow for a photo to be taken, but the console's larger processing power and the Wiimote's abilities makes for richer content. Unlike the handheld versions, the console version has students walking around the school, has a sign outside the school ground that is readable, and contains slightly more complex versions of some of the mini-games. When putting together the avatar, the Wii version also allows the player to select different color designs for the outfits, an option not offered in the handheld versions.
Ghoul Spirit starts with requesting the player to create their student avatar to navigate the digital Monster High with. Players can choose from a selection of six monsters - mash-up monster, vampire, werewolf, mummy, zombie, and gorgon - several facial design, several skin colors, several haircuts, two outfits, and in the Wii version several outfit color designs, to put together their avatar. A name also needs to be chosen, which can be one the player creates themself or selects from a generator.
Once the avatar has been created, it is spawned in the office of Headless Headmistress Bloodgood and the player is required to pick up their student ID from a nearby machine. From this point, the actual game starts. The gameplay is divided over six regular student missions, one secret student mission, one Freaky Flaw mission, and five assignments by the teachers. The student missions make up the bulk of the gameplay and can be done in whichever order the player chooses, though only one mission can be active at a time. The assignments can be done at any moment the player so chooses, but the secret student mission and the Freaky Flaw mission need to be unlocked by completing regular student missions.
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The diary is a tool in the game to keep track of the player's relations with the students and teachers. It has 22 entries, of which six for teachers. The quality of the relation is displayed by means of a gauge: the fuller it is, the better the relation. While the relations with the main characters and the teachers follow from completing chapters and going to classes, the gauges for relations with the other students seem to fill up for no reason at all. The game doesn't even allow the player to interact with Abbey and Spectra and still their relation gauges will fill up too.
Aside from the gameplay use, the diary also holds small notes on all 22 characters mentioned. Some of these reveal information found only in Ghoul Spirit, or at least at the time of the game's release. Each student also has a secret second note that needs to be unlocked with a code, though Spectra's is unlocked by default. Some of these codes could be found at the Monster High YouTube channel, which put up a Video Game playlist of eight shorts. At the end of these shorts, codes are given out. Clawdeen's code (1331) and the player's code (1333) unlock the Growlicious Pets Locker Sticker Pack and the Skull-Tastic Locker Sticker Pack respectively, while 1329 unlocks the Ghouls Rule Locker Sticker Pack and 1330 unlocks the Fab Pets Locker Sticker Pack and 1332 unlocks the Fear Squad Locker Sticker Pack, but the other codes unlock extra notes on the relevant characters. A particular oddity is Toralei's code, which upon entry claims a note for the Werecat Twins has been unlocked. This appears a leftover from an intent to give the Werecat Twins their own entry in the diary, which was scrapped before release.
- Clawdeen - Clawdeen blogs about DIY projects. Her younger sister is Howleen. (1313)
- Cleo - Cleo always needs her royal bandages! Cleo is scared of the dark. (1318)
- Lagoona - Her parents are the oldest monsters. Chlorine dyes her hair green and blue. (1324)
- Frankie - Her first words were "Brain Freeze!" She has one green eye and one blue eye. (1314)
- Toralei - Tora is Japanese for "tiger" (TORAlei). She quit fearleading because of Cleo. (1326)
- Draculaura - Her father was a Roman Centurion. Her mom was Dracula's normie servant. (1323)
- Heath Burns - He is on the track team with Clawd and Deuce. His head sparks fire when he's excited. (1325)
- Deuce - His hometown is Petros Island, Greece. He has 2 aunts in Greece: Euryale and Stheno. (1315)
- Ghoulia - Her favorite comic is "Dead Fast". Her eyelids blink one at a time. (1319)
- Mr. Where - Named Stage and Scream magazine's "Deadliest Drama King" three years in a row. Teaches Drama in the Vampitheater.
- Slo Moe - SloMoe's real name is Moe Deadovitch. Ghoulia has a big crush on SloMoe. (1321)
- Ms. Kindergrubber - Has a Bachelor's Degree in Candy Construction. Teaches Home Ick.
- Holt Hyde - Holt's mom and Heath's dad are siblings. He normally comes out at night. (1322)
- Headless Headmistress - Has a horse named Nightmare.
- Mr. Hack - "A dull mind cannot cut the cheese of knowledge." - Favorite Quote. Teaches Mad Science.
- Mr. Mummy - "Knowledge is the cure for every curse." - Favorite Quote. Teaches Clawculus.
- Clawd - He and Draculaura make a cute couple. No dumb jock–Clawd loves competition! (1320)
- Coach Igor - "You can't hide from fitness!"
- Operetta - She plays rockabilly and blues guitar. Her dad teaches keyboard class at MH. (1327)
- Abbey - She isn't afraid to call it like it is. Her favourite sport is snowboarding. (1317)
- Spectra - She has an anonymous column in the school paper. She is a ghost from the 19th Century.
- Jackson - He likes to play casketball at MH. He is the only human at Monster High. (1316)
The Nintendo Gamer issue of December 2011 gave the DS version of Ghoul Spirit a score of 50 out of 100. In general, the Wii version has received better appreciation than the DS an DSi versions.
- One of the chambers in the game is the Vampitheater, which appears to be just another name for the Auditorium. It is possible the two are not the same area of Monster High though, since the stage in the webisodes sometimes does and sometimes doesn't feature a runway.
- The Mad Science potion-making quests reveal that unicorns, lovebirds, ogres, jackalopes, gremlins, goblins, Pegasus, the Hydra, the Phoenix, the Kraken, the Scylla, the Charybdis are canon to the Monster High universe.
- Despite a gorgon's stare being able to petrify people by looking at them, the gorgon avatar does not wear sunglasses(But it was confirmed that not all gorgons can turn people to stone).
- The game features a chapter dedicated to Lagoona Blue, but not one dedicated to Deuce. In contrast, the game offers the option to play as a gorgon, but not as a sea monster.