Best friends Mikan and Hotaru grew up in a small town in the remote countryside. When Hotaru moves to a school for geniuses in Tokyo, Mikan misses Hotaru so badly that she decides to travel to Tokyo herself to find Hotaru. She finds Hotaru in a school called "Alice Academy," and finds that the school is actually for people with special powers called "Alices." Narumi-sensei, a teacher at the school, discovers that Mikan also happens to have an alice, and Mikan is permitted into the academy.

Mikan Sakura (佐倉蜜柑 ,Sakura Mikan?) Voiced by: Kana Ueda
The cute and (overly) energetic Mikan lives only with her grandfather and attends a run-down elementary school. Upon hearing that her best friend, Hotaru Imai, is off to another school, it didn't take long for Mikan to decide that she will literally follow Hotaru everywhere she goes. Mikan discovers that the new school, Gakuen Alice, is rather a special one. As it was tried and tested, Mikan can actually nullify any kind of Alice force thrown at her. As a result, Mikan is like a walking barrier that no one can affect. It is for this reason that she is being closely watched by the school.[3] Naturally, Mikan had a hard time adapting to her new school life but her outgoing and sincere personality eventually wins them over. She manages to turn everyone into friends and even admirers. The only person she can't seem to understand her feelings very well towards is Natsume. But, she definately shares the same feelings that he has for her. She wants to see her grandfather so she gives the letters to Narumi but she found out that he has been keeping them.

Hotaru Imai (今井 蛍 ,Imai Hotaru?) Voiced by: Rie Kugimiya
Hotaru Imai is Mikan's best friend[4]. She is extremely intelligent and rational. During the story, though she may appear to be rather cold and indifferent on the surface, it is apparent that she genuinely cares for Mikan. She has the Alice of Invention[5], and during her time at the country with Mikan and her grandfather, she created many strange but useful inventions, often made to look like animals. Hotaru breaks the fourth wall by teaching the audience about her inventions. The other characters see her explaining her inventions to apparently no one. It may be that she has a crush on Ruka.

Natsume Hyūga (日向 棗 ,Hyūga Natsume?) Voiced by: Romi Park
Stoic and scary, Natsume may be icy on the outside but is actually fiery on the inside. Born with the Fire Alice[5], Natsume is hated and feared by many students and teachers because of his dangerous ability. Natsume is often seen with his best friend, Ruka. Other than Ruka and Youichi, the fire starter didn't really get along well with the others until Mikan came along. At first, her optimistic nature was like a poison to him but gradually, he softened up to her and going as far as developing romantic feelings for her. Natsume's past is shrouded with mystery and nobody really knows what goes on in his mind. But one thing is for sure, he is extremely suspicious of the adults in the academy. He is involved with the school's secret missions for reasons unknown. Though he really doesn't like doing it, the threat to endanger his classmates and especially Mikan's welfare forces him to be at their mercy. They do that because they know that Natsume would give his life for her.

Ruka Nogi (乃木流架 ,Nogi Ruka?) Voiced by: Miwa Yasuda
Ruka is Natsume's childhood friend and often referred by Mikan throughout the story as "Ruka-pyon". He is a gentle and generous person, characteristics that balance out Natsume's personality. His animal pheromone Alice allows him to get along with animals[5], a fact that he is embarrassed of and often blackmailed over by Hotaru. Despite this, he often carries a rabbit with him. He knows Natsume (his best friend) has a crush on Mikan, and he also has a crush on her. In episode 19, Ruka plays Snow White in a play and Mikan was forced to play the prince. But at the very end, Narumi told her to improvise and kiss him on the lips, Natsume threw an apple at Mikan to stop her in fits of jealousy. They all 4 become best friends...!