Our research involves of how Paraguayan migrants who are living in Misiones, Argentina, manage medicinal plants in home gardens, and how this practice can be related to the landscape. We examine the relationship between the richness of home garden medicinal plants and landscape variables (e.g., distance to the forest) by applying PLS analysis, which combines principal component analysis with linear regression. We surveyed 60 home gardens localized in a rural area, and we characterized the surrounding landscape with geospatial tools. Paraguayans’ home gardens are extremely diverse sites (total of 136 medicinal species), where both native (82) and introduced species (50) are managed. People who live close to the native forest or mixed use areas (e.g., farms, secondary vegetation) tend to possess less native plants in their gardens because they are available nearby. While gardeners, who live in proximity to tree crops (e.g., pine plantations), have reduced access to wild medicinal resources; therefore, their effort is concentrated on maintaining native plants. These results reflect a relationship between accessibility to medicinal plants in the landscape and the management practices in the home gardens, a neglected driver in explaining the richness and composition of the medicinal plants in home gardens so far. Thus, we contributed evidence in support of the environmental scarcity compensation hypothesis. Finally, our study supports the idea that home gardens appear to function as a springboard for plant domestication.