Of Mice and Men is not kind in its portrayal of women. In fact, women are treated with contempt throughout the course of the book. Steinbeck generally depicts women as troublemakers who bring ruin on men and drive them mad. Curley's wife, who walks the ranch as a temptress, seems to be a prime example of this destructive tendency—Curley’s already bad temper has only worsened since their wedding. Aside from wearisome wives, Of Mice and Men offers limited, rather misogynistic, descriptions of women who are either dead maternal figures or prostitutes.

Despite Steinbeck’s rendering, Curley's wife emerges as a relatively complex and interesting character. Although her purpose is rather simple in the book’s opening pages—she is the “tramp,” “tart,” and “bitch” that threatens to destroy male happiness and longevity—her appearances later in the novella become more complex. When she confronts Lennie, Candy, and Crooks in the stable, she admits to feeling a kind of shameless dissatisfaction with her life. Her vulnerability at this moment and later—when she admits to Lennie her dream of becoming a movie star—makes her utterly human and much more interesting than the stereotypical vixen in fancy red shoes. However, it also reinforces the novella’s grim worldview. In her moment of greatest vulnerability, Curley's wife seeks out even greater weaknesses in others, preying upon Lennie’s intellectual disability, Candy’s debilitating age, and the color of Crooks’s skin in order to steel herself against harm.