Lithospermeae Dumort., a tribe under the subfamily Boraginoidae, is a perennial herb containing approximately 470 species under 26 genera, primarily distributed in temperate and tropical regions. To gain a deeper understanding of the medicinal plants of Lithospermeae and better protect and develop plant medicinal resources, the phytochemistry, pharmacology, and traditional use of Lithospermeae with medicinal value were analyzed. Phylogenetic analysis was carried out based on the internal transcribed spacer sequence. Through spatial analysis and the species distribution model, the spatial distribution pattern of Lithospermeae medicinal plants was analyzed. Meanwhile, the relevant targets and pathways involved in the pharmacological effects of commonly used medicinal plants were predicted using network pharmacology to further explore the genetic origin of Lithospermeae and enrich the pharmaphylogeny of medicinal plants. In this study, the chemical composition, traditional efficacy, and modern pharmacological activity of Lithospermeae were collected for the first time and analyzed in combination with the geographical distribution model, molecular phylogeny, and network pharmacology. Based on our findings, the pharmaphylogeny of Lithospermeae was preliminarily discussed, providing the scientific basis for basic research regarding Lithospermeae. Concurrently, this study explored the relationship between the development of the regional medicinal plant industry and the protection of biodiversity. Furthermore, our findings provide direction and theoretical guidance for the study of the phylogenetic relationships in medicinal plants and the development of Lithospermeae medicinal plant resources.