<p>The Doctrine of signature suggests there are parallels between a plant’s appearance, structure, or therapeutic functions that it may have on the corporal systems of the human body as well as the disease it treats. This concept, often considered more of a traditional belief than an established scientific theory has been dismissed as primitive and unscientific or as a mnemonic aid. However, direct tests of these theoretical predictions are rare, suggesting most of these criticisms are premature. We tested one of the most popular doctrine of signatures that red sap plants treat blood disorders. We systematically reviewed the literature for a comprehensive list of red sap-containing plant species across the world, randomly selected 200 other plant species without red sap in the same regions, and recorded the medicinal uses of all species. We demonstrate that species containing red sap were three times more likely to be used in the treatment of blood-related disorders. In addition, similarly to plant species used in the treatment of blood disorders, species with red sap were also phylogenetically close. This strong relationship is most likely due to red quinones often present in plants with red sap which are known for their efficacy in wound healing. Our straightforward approach can be used by ethnobiologists for more tests of other doctrines of signatures. It is important to establish a mechanistic understanding of the links between signature, plant secondary chemistry, and therapeutic efficacy.</p>