Misao had been missing for three months when Aki awoke to the sound of their classmate's voice. Most of their peers thought Misao to be dead. When a mysterious earthquake shakes the school Aki goes to, they and their classmates - as well as their homeroom teacher Mr. Sohta - are teleported into another dimension. Aki's classmates blame Misao's Curse and Aki sets out to collect the six missing parts of Misao's body to break the curse. (Spoilers warning!)
Aki was selected exclusively by Misao to find her and redeem her soul. This is because Aki had at least one interaction with her in the entirety of being classmates, none of which seemed to be negative. As no one really talked to Misao besides to condescend, Aki was the only one to talk to her in an inviting dialect. Misao first contacts Aki by appearing through dreams, and after sending the school into The Otherworld, Aki has visions/hallucinations of Misao's words; "HELP ME FIND ME" strewn about in a repeating pattern, written in blood.
She is also most likely completely insane, seeing as when a character is brutally murdered by a man with a chainsaw, she is completely unfazed. Along with her also watching another classmate be run over by a car.
Ayaka is a minor character in Misao. She has a crush on the teacher, Mr. Sohta. After being teleported into The Otherworld, the player can find Ayaka in the teacher's office, snooping around Mr. Sohta's desk. Still obsessed, Ayaka tells the player that she found love letters to 'HER' Mr. Sohta, and ignores the player's advice to find somewhere safe to hide.
Later in the game, Mr. Sohta and Ayaka are found in the same room, with Mr. Sohta telling the player that Ayaka is still in shock after being attacked by a monster. He then asks the player to get a tranquilizer out of his desk, and when the player returns, Ayaka is dying, with Mr. Sohta saying the monster came back and he couldn't protect her. At the end of the game, it is revealed that Mr. Sohta was the one who killed Misao, and killed Ayaka because she found Misao's arms in his desk.
Misao is the tragic heroine and titular character of the game. She is noted throughout the game as being friendless and lonely. Misao was bullied by a group of girls led by Yoshino, had her diary posted on the school bulletin board, and went "missing" three months before the game began (at the end of the game it is discovered that she was murdered by Mr. Sohta.) Finally, she has come to take her revenge on those who hurt her while she was alive. She cursed the school and sent it into The Otherworld, though allows Aki to undo the curse because Aki has never hurt her. To undo the curse, her 6 body parts must be sacrificed on an altar, with 6 people murdered as well. Misao kills five, but the sixth is left up to the player, with Tohma and Mr. Sohta as the two options.
Library is the fictitious vice-president of the Student Council and most likely the assistant of Onigawara. She is also a guiding force in the game much like Onigawara and a minor/supporting character. Like Aki, players can name her, though Novella is her default name. She does not have many (any) other friends. Library is believed to be the clone of Aya we see at the end of Mad Father.
Kudoh is Aki's classmate and Misao's childhood friend. The two grew apart as they became older. Kudoh distanced himself from Misao due to the fact that his class mates made fun of him for hanging out with a girl, and that Yoshino was bullying Misao and that Kudoh didn't want to also be bullied, similar to Aki.
He was the classmate of Misao until she mysteriously disappeared. Misao had romantic feelings for him, and it is hinted that he returned them, even though he was Saotome's boyfriend. He seems to be quite tough, but abandons Saotome at the hands of a monster instead of attempting to save her.
Saotome was a classmate of Aki and Misao. She was also part of the group of girls that tormented Misao, and was the girlfriend of Tohma before he abandoned her to die at the hands of a monster.
Yoshino was the leader of the bullies in Aki's and Misao's school. She can be considered a minor/supporting character in the game, but she was a major player in Misao's disappearance and eventual death.
Mr. Sohta is the former teacher of Aki's class. He is known by his students to be a "kind and caring" teacher, when in reality this is false. He is described as a suave and handsome man. He seems to have a hand fetish as well. Sohta wears a suit as his work uniform and parts his sand colored hair. While he was still attending high school, Sohta was considered unattractive and was bullied for it in school. Since he had no friends in high school any positive relationship was everything to him, this explains why he almost instantly fell in love with the girl who ate lunch with him, he was simply in love with the thought of being treated well. This is what 'pushed him over the edge' and explains why he treats girls the way he does, if they seem to truly like him, as Misao did, he becomes phsycotic and will have them no matter what, this leads some players to believe that he is a yandere that was bullied into his own insanity. He was Misao's killer, and if Tohma is killed near the end, Mr. Sohta pushes the player off the roof in order to prevent anyone from knowing the true him.
Onigawara is the fictitious student council president at Aki and Misao's school and a supporting character in the Misao game who guides the player in the same manner as Library. He is used as a save point, and is the same character as Ogre in Mad Father.
WARNING! SPOILERS BELOW! Read at your own risk.
If you choose to kill Tohma, Mr. Sohta will push Aki off of the rooftop. The last scene is a girl named Miho going up to Mr. Sohta and saying that she got in a fight with her friend, Maho. Mr. Sohta will comfort Miho in the same way he was sweet to Misao before killing her, and the player will be redirected back to the tittle screen, with Miho presumably being murdered and starting the mayhem again.
If you kill Mr. Sohta, Misao will use her last strengh to show Aki how she died.