An unnamed fifteen-year-old diarist, whom the novel's title refers to as Alice, starts a diary. With a sensitive, observant style, she records her adolescent woes: she worries about what her crush Roger thinks of her; she loathes her weight gain; she fears her budding sexuality; she is uncomfortable at school; she has difficulty relating to her parents. Alice's father, a college professor, accepts a teaching position at a different college and the family will move at the start of the new year, which cheers Alice up.
The move is difficult. While the rest of her family adjusts to the new town, Alice feels like an outcast at school. Soon she meets Beth, a Jewish neighbor, and the two become fast friends. Beth leaves for summer camp and Alice goes to live with her grandparents. She is bored, but reunites with an old friend, Jill, who invites Alice to a party. At the party, Alice unwittingly drops LSD and experiences a fantastic drug trip. Though curious, she vows not to do drugs again.
Alice happily experiments with more drugs and loses her virginity while on acid. Roger and his parents show up unexpectedly to visit her grandfather, who has had a small heart attack. Alice is enthralled with Roger but feels guilty about her drug use and loss of virginity. She doesn't know to whom she can talk about drugs. She is worried that she may be pregnant. Alice goes home and her family accepts her warmly. Unable to sleep, she receives powerful tranquilizers from her doctor. Beth returns from camp, but Alice finds that Beth has changed. In a boutique, Alice meets Chris, a hip girl. Alice's parents worry about Alice's "hippie" appearance.
Alice and Chris are both dissatisfied with the establishment and their own families. Alice gets a job working with Chris, and the two become best friends. At school, they use drugs and are popular. Chris's friend Richie, a college boy, turns Alice on to marijuana. To make more money for drugs, she and Chris sell drugs and do whatever they can to help Richie and Ted (Chris's boyfriend and Richie's roommate). Alice and Chris discover Richie and Ted having sex with each other and flee to San Francisco. Alice turns Richie in to the police and vows to stay clean with Chris. They move into a cramped apartment. Chris secures a job in a boutique with a glamorous older woman, Sheila, and Alice gets one with a custom jeweler. Sheila invites the girls to a party at her house.
At Sheila's swanky party, the girls use drugs again. They continue to party with Sheila until one night, when trying heroin, Alice realizes that Sheila and her boyfriend have been raping and brutalizing them. The girls kick their drug lifestyle. They find a new apartment in Berkeley and open a jewelry shop there, which turns into a hangout for the neighborhood kids. Alice misses her family. She returns home for Christmas, and the holiday spirit and family camaraderie revive her. She begins school and resists drug advances from old friends, though some are aggressive. Chris smokes marijuana with her, and Alice goes back on drugs. The police raid Chris's house while she and Alice use drugs. The girls are put on probation, and Alice will be sent to a psychiatrist.
Alice continues to do drugs without her family's knowledge. She hitchhikes to Denver (recording her diary entries on scraps of paper without dates). She travels to Oregon with other drug users but soon loses them. A janitor directs her to a mission similar to the Salvation Army. Alice is cleaned up and meets a young sufferer of lifelong sexual abuse, Doris, who lets her stay at her apartment. They get sick from malnourishment and hitchhike to Southern California, where Alice takes more drugs, even prostituting herself for them. Alice talks with a priest about teen runaways, and he calls her parents. They want her to come home. In the city, Alice meets several other runaways and talks to them about why they left home. She imagines she may go into child guidance or psychology some day to help out others, and she vows to quit drugs.
Alice comes home and is excited to renew her life with her family. Alice loses consciousness and drifts off into a reverie that she thinks is either a flashback (caused by LSD residue in the spinal cavity) or a schizophrenic episode. Otherwise, Alice is happy with her family and with herself, except for her social isolation: she can't hang out with drug users, and "straight" kids don't want her around. Alice's grandfather dies in a coma from a stroke. She agonizes over the thought of worms and maggots eating his dead body underground. Her relationship with her father matures. Someone plants a joint in Alice's purse, and she leaves school to go to his office. He consoles her, and gets her permission to study at the university library.
Alice meets a freshman at the university library, Joel; his father is dead, his mother is a factory worker, and he works as a janitor to pay for school. He and Alice get to know each other better, as does her family. She fantasizes about marrying him. Pressure to use drugs at school intensifies, as the kids harass Alice and her family. Alice's grandmother dies. After the funeral, Joel has a long talk with her about death that makes her feel better, and they kiss. She opens up to Joel about some of her past, and he is kind and supportive.
Alice writes in her undated diary from a hospital. She is unsure how she has ended up here and can only think of the worms she thinks are eating her alive. She has chewed her fingers to the bone, and clawed up her face and body. Her father says that someone dosed with LSD the chocolate-covered peanuts Alice was eating while she was baby-sitting. Alice finds out she is being sent to an insane asylum. Her father tells her that when her case was brought before a juvenile court and that Jan and another girl testified that Alice had still been on drugs and was selling them. Alice registers at the State Mental Hospital. She is frightened by the ugly building and by the inmates. She meets a little thirteen-year-old girl, Babbie, a former prostitute and drug user with a history of sexual abuse.
Life in the asylum drains Alice. A visit from her parents brings a warm letter from Joel. Her father reports that Jan has retracted her statement, and they're trying to get the other girl to do the same to free Alice. Alice returns home and is happy to be with her family. The family takes a vacation together, and when they return, Alice is invited swimming by Fawn, a "straight" kid. She has a fun time with Fawn's friends and hopes that they haven't heard stories about her. Joel makes a surprise visit and gives her a friendship ring, which she vows to wear her whole life. She is worried about starting school again but feels stronger with the support of her new friends and Joel. She comments that she no longer needs a diary, for she now has people in her life with whom she can communicate.
In the epilogue, we are told that Alice died three weeks later of an overdose—whether it was premeditated or accidental remains unclear—and that she was one of thousands of drug deaths that year.
Alice isn't the name of the character, 'Go Ask Alice' is a lyric from a song called 'White Rabbit'.