Collin Fenwick, the narrator and main character of The Grass Harp, comes to live with the Talbo sisters after losing both parents at the age of eleven. Struggling with his mother's death and his father's intense emotional turmoil, Collin is already emotionally withdrawn when Verena Talbo steps in to take charge of his life. Initially intimidated by Verena, Collin feels like an outsider in the Talbo household. However, Dolly and Catherine eventually offer him the familial connections he longs for. The novel's events, mostly occurring when Collin is sixteen, guide him to understand himself and his relationships better. Despite this growth, and perhaps due to Dolly's significant impact on his character, Collin remains an outsider in the community, never becoming a businessman like Riley Henderson or a political leader like Junius Candle, who seem to contrast with him.

Initially, Dolly Talbo is uncertain about the wisdom of raising Collin in a household of women. However, she soon welcomes him, allowing him to join her and Catherine on their trips to the River Woods to collect roots and herbs. Dolly's mail-order clients commend her "dropsy cure," yet her shyness makes her an outsider in the community. Her neighbors often perceive her as mentally slow, and her peculiar behavior has been a topic of discussion even before she and her friends decide to live in a treehouse. Although she has never opposed Verena's "household rules" before, Dolly insists on keeping "the cure" for herself, stating that it's the one thing she has ever withheld from her sister.

Despite her influence, Verena Talbo is also an outsider in the town. The townsfolk respect and fear her, but they don't truly like or accept her due to her abrasive demeanor and constant frown. Moreover, she is an outsider in her own home, where Dolly and Collin try to avoid her, and Catherine derisively calls her "That One." Verena's efforts to form emotional connections fail repeatedly: her friend Maudie Laura Murphy leaves to marry a liquor salesman and eventually runs a gas station near the Grand Canyon; Dr. Morris Ritz, who could have been her soulmate, steals her money and escapes to Paraguay; Dolly agrees to return home but refuses Verena's plans to show her the ocean; and Collin opts for law school over traveling the world with Verena. Following these rejections, Verena loses interest in both business and life.

Arguably the most peculiar figure in the novel is Catherine Creek. She claims to be of Indian descent, although the townspeople are convinced she is actually African-American. Already marginalized due to her race, Catherine further distances herself by her unusual attire and odd habits. The most striking of these is her tendency to stuff her cheeks with cotton, making her speech intelligible only to Dolly and Collin. This communication barrier contributes to her arrest, but more crucial is Catherine's belief that one should learn which matters to keep private. Unlike Verena, Catherine has always understood that Dolly is the core of her existence, showing unwavering loyalty by stealing a bird's egg for her and turning down a peculiar marriage proposal from Bill in Miami. After Dolly's passing, Catherine withdraws to her cherished cabin with only Dolly's radio for company.

Judge Charlie Cool is the fifth key character, describing himself and Dolly as "accepters of life [who] grant its differences—and consequently are always in trouble." He tells his fellow tree-dwellers that being labeled as fools by the town has liberated them to discover their true selves and explore the essence of love—"that love is a chain of love, as nature is a chain of life."...