Teddy is a decorated World War II veteran currently serving as a U.S. Marshal. He arrives at Ashecliffe Hospital to investigate a missing patient, though his cynical exterior hides deep psychological trauma from his wartime experiences—particularly the liberation of Dachau—and the death of his wife in an apartment fire. He suffers from debilitating migraines and vivid dreams of his deceased wife. Beneath his official law enforcement duties, he harbors a hidden motive to find the arsonist responsible for his personal tragedy.

Chuck is Teddy's newly assigned partner in the U.S. Marshals service. He is affable, highly observant, and quick to establish a comfortable rapport with Teddy. As the hurricane traps them on the island and the investigation grows stranger, Chuck provides a grounded perspective, though he soon begins to suspect they have walked into a dangerous trap designed by the hospital staff.

Dr. Cawley is the legendary chief of staff at Ashecliffe Hospital. He is a prominent psychotherapist who strongly advocates for talk therapy over the harsher surgical treatments of the era. While he presents himself as a cooperative professional, his slick demeanor and protective stance over his staff files make him a prime suspect in Teddy's eyes.

Rachel is a deeply delusional patient at Ashecliffe Hospital who was institutionalized after drowning her three children. She believes she is still living in her Berkshire home and that the hospital staff are merely deliverymen. Her seemingly impossible escape from a locked room, leaving behind cryptic numerical codes, forms the central mystery of the marshals' visit.

Dolores is Teddy's deceased wife, who died tragically in an apartment fire two years before the events of the novel. She lives on through Teddy's intense, recurring dreams and memories, often speaking to him in cryptic warnings. Her death remains the driving force behind Teddy's emotional instability and his secret quest for revenge against the arsonist who killed her.

Andrew Laeddis is an arsonist who started the tragic apartment fire that killed Dolores Chanal. Teddy believes Laeddis is currently incarcerated at Ashecliffe Hospital due to his violent, mentally ill nature. Laeddis represents the source of Teddy's deepest grief and serves as the primary reason the marshal accepted the Shutter Island assignment.

Dr. Sheehan is a psychiatrist at Ashecliffe Hospital who led the group therapy session Rachel attended before she vanished. The marshals discover that he left the island for a vacation the morning after her disappearance, making him unreachable and immediately casting suspicion on his potential involvement in her escape.

George Noyce is a former college student who developed schizophrenia after participating in a psychiatric drug trial. He was sent to Ashecliffe, where he suffered greatly. Prior to the events of the novel, he served as Teddy's informant, describing illegal human experiments on the island and giving Teddy a reason to investigate the hospital.

Dr. Naehring is a German immigrant and the chief liaison to Ashecliffe's board of overseers. He strongly advocates for the use of psychotropic drugs to treat mental illness. His aggressive, parlor-trick psychoanalysis of the marshals immediately irritates Teddy, reminding the veteran of his traumatic wartime experiences.

The warden is the strict head of security at Ashecliffe Hospital. He oversees the armed guards, the electric fences, and the protocols keeping the dangerous patients contained. He holds dark views on human nature, philosophically believing that violence is an intrinsic, unchangeable part of humanity.

McPherson is a dutiful security official at Ashecliffe Hospital. He gives the marshals their initial tour of the island's three wards and enforces the strict rule that all visiting law enforcement must surrender their firearms while on the premises.

Bridget is a patient at Ashecliffe who was institutionalized after murdering her abusive husband. During her interrogation, she appears heavily coached by the hospital staff regarding Rachel's actions, but she manages to secretly write the word "run" in Teddy's notebook when Chuck steps away.

Peter is an Ashecliffe patient who severely injured his father's nurse. He remains completely in denial about his own violent actions and speaks with disgust about Rachel Solando's crimes, believing himself to be fundamentally different from the rest of the institutionalized population.

Mr. Ganton is an orderly working at Ashecliffe Hospital. He was the last staff member to see Rachel Solando before she vanished, having locked her securely inside her room for the night. His testimony makes Rachel's escape appear physically impossible to the marshals.

Trey is an orderly at the hospital who temporarily shares a room with Teddy when the marshals are forced to wear staff scrubs due to the weather. Teddy later intimidates him into revealing information about the broken security fences and ferry schedules.