Traditional medicines have been used by Aboriginal Australians for countless generations. Many Traditional Knowledge Holders are seeking to commercialise this knowledge and make it available to consumers. Although the beneficial effects of Traditional Medicines have been passed down through many generations, in most cases, the mechanism of action and molecular targets of these medicines are still not identified. We will describe the use of native mass spectrometry (MS) for the target identification process. Native MS allows the detection of proteins in their native state. If the ligand binds to a protein target, an additional peak for the protein-ligand complex will appear in the spectrum. The difference between the protein peak and the protein-ligand peak enables the determination of the charge state of the protein, allowing calculation of the exact molecular weight of the target protein.