Except for the first chapter (set in 1981), the narratives follow a loose chronology. Each chapter is narrated by a different character. These narratives are conversational, as if the narrators were telling a story, often from the first-person perspective. There are, however, five chapters that are told from a limited third-person perspective. The conversational tone of the novel is representative of the storytelling tradition in Native American culture. It draws from Ojibwa myths, story-telling technique, and culture. It also incorporates the Euro-Indian experience, especially through the younger generations, some of whom have been forced by government policy to accept, if not possess, Euro-American culture.
Love Medicine begins with June Morrissey freezing to death on her way home to the reservation. Although she dies at the beginning, the figure of June holds the novel together. Similarly, a love triangle among Lulu, Marie, and Nector is a link among the narratives, even though it is not a persistent theme in the novel. There is also a homecoming (or homing) theme in the novel. The use of multiple themes adds to the storytelling effect of the work. Other themes include: tricksters (in the Native American tradition), abandonment, connection to land, searching for identity and self-knowledge, and survival.