Meg is a 14-year-old high school student who wears glasses and has mouse-brown hair. She feels insecure about her appearance and intelligence compared to her mother's scientific accomplishments. She has a quick temper and struggles socially, but she is fiercely loyal and protective of those she loves.

Charles Wallace is Meg's six-year-old brother and a first-grade student with blue eyes. His genius-level intelligence and unusual interests alienate him from his peers, making him a frequent target for school bullies. He possesses strong intuition, allowing him to sense others' emotions and thoughts. He currently suffers from a worsening, unexplained illness.

Calvin is a tall, blue-eyed, 15-year-old redhead and a high school senior. He is a star basketball player and senior-class president, highly popular at school but unappreciated by his impoverished family. He finds safety and validation at the Murry household and offers steady, empathetic support to Meg.

Mr. Jenkins is a middle-aged man with thinning brown hair, horn-rimmed glasses, and dandruff on his suit. Formerly the high school principal, he now oversees the village elementary school and expresses irritation at dealing with the Murry children again. He projects apathy to mask his deep-seated insecurities and fear of failure.

Proginoskes is a cherubim who appears to human eyes like a feathery sphere with hundreds of wings and eyes. He is a Namer, tasked with knowing the true identities of stars and creatures. Though initially resentful of working with earthlings, he serves as Meg's guide and communicates through telepathic thought called kything.

The Echthroi are destructive entities that seek to extinguish stars and un-Name creatures, making them forget their identities. They act as parasites, feeding on hate and attempting to turn everything into nothingness. They directly target Charles Wallace's cellular health to destroy him from the inside.

Louise is a large, gentle black garden snake living on the Murry property. Named by the twins after a family friend, she possesses unusual intelligence and communicates silently with those around her. She provides a steady presence of comfort and council without directly joining battles.

Mrs. Murry is a beautiful scientist studying microscopic cellular biology. She works from a laboratory inside the family home. She worries over Charles Wallace's declining health while managing the household during her husband's absence.

Mr. Murry is a physicist traveling to Brookhaven to consult with other scientists. He investigates a cosmic phenomenon involving strange sonic sounds and rips in space that cause stars to disappear.

Sandy is one of Meg and Charles Wallace's older twin brothers. He is practical and grounded in normal human reality, making him highly skeptical of the unusual events his younger siblings describe.

Dennys is Meg and Charles Wallace's other twin brother. Like Sandy, he relies on extreme pragmatism and questions concepts that break the laws of known physics or everyday perception.

Dr. Colubra is the family's trusted physician and a close friend of Mrs. Murry. She attempts to diagnose and treat Charles Wallace's mysterious illness, suspecting it relates to his mitochondria.

Blajeny is a Teacher from the distant galaxy of Veganuel. He recruits Meg, Calvin, Charles Wallace, and Proginoskes into his cosmic classroom, assigning them tasks necessary to save Charles Wallace's life.

Sporos is a young farandola born inside one of Charles Wallace's cells. He is arrogant and resistant to maturing, expressing intense disdain for being hosted by an earthling.

Senex is a mature fara rooted inside Charles Wallace's mitochondria. He is the organism from which Sporos was born and suffers from energy loss due to the chaotic behavior of the younger entities.