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Histories of botany highlight relationships between natural history and European exploration of and expansion in the Atlantic World emphasizing bioprospecting, botanical exchange, and their importance for the evolution of extractive modes of labor and economy (slavery and plantation economies). The Eastern Mediterranean was also a sight of botanical exploration in the eighteenth and nineteenth centuries, although this history is underexplored. The polities of this region had a long and shared history of knowledge production, of trade, of political relations, and of monotheism. While the ‘New World’ represented novelty and held great wonder for European explorers, the Eastern Mediterranean, while perhaps not thoroughly and completely ‘known’, was familiar to them and was refracted through multiple shared traditions such as antiquity and the biblical tradition. This paper considers histories of botanical collecting in the Eastern Mediterranean during the eighteenth-twentieth centuries—a vibrant era of knowledge production when disciplinary boundaries in the observational sciences developed. I discuss the Royal Danish Expedition to Yemen (1761-1767) and the independent collecting enterprise of P. E. Botta (1802-1870), naturalist-voyageur for the Paris Museum of Natural History. These expeditions are connected by their bioprospecting itineraries. What guiding principles and instructions did naturalists use to collect the region’s flora? Did their findings shape scientific views of the boundaries between different biogeographic regions of flora? Examining histories of natural history can help bridge gaps between humanists and scientists and open spaces for collaboration especially in light of contemporary concerns about extractive practices associated with natural history collections.