Disaffected, confused, and depressed mothers populate the pages of Walk Two Moons with alarming frequency. Mrs. Winterbottom, Sal's mother, and Ben's mother all experience depression or mental stress severe enough to affect their day-to-day lives. Mrs. Winterbottom and Sal's mother are both clearly troubled by their role as mother and wife, and the struggle to understand how their pasts and their "true selves" relate to these roles results in confusion, depression, and the need to be alone. Through the suffering of these women, Creech draws attention to the stress and disappointment involved with the sense of being confined to a role or of living an insignificant life.
The messages, postcards, and journal entries embedded in the text of Walk Two Moons all demonstrate the uncertainty and difficulty involved in interpreting the words of others. Phoebe twists the benign and comical messages left on her doorstep into series of threats or mysterious clues hinting at Mrs. Winterbottom's whereabouts. Mr. Birkway, who argues with his students that ambiguity is one of the greatest beauties of written texts, sees the journals they have written as "brilliant" examples of conflicting emotions, whereas his students see them as embarrassing revelations of their most private thoughts. Sal struggles to interpret the conflicting message of the postcards her mother sends her. Each postcard expresses love for Sal, and yet reminds Sal that her mother needed to leave her to take a long, soul-searching trip. Throughout the novel, Sal becomes more and more skilled at understanding and accepting these ambiguities.
Throughout the novel, the characters use journeys as a means of both escaping from a painful present and of invoking confrontation with the source of their trouble. Sal's mother and Phoebe's mother leave home to come to terms with their doubts about their pasts and their roles. Sal leaves home first to reverse and later, she realizes, to concretize her mother's death. Each character uses a physical journey to induce an emotional journey, which will, they hope, allow them to live more truly and fully in their original roles.