Vector-borne diseases cause more than 1 million deaths annually. The research of new medicines is urgent, especially since there is currently no specific treatment. In this study, the authors have selected 64 endemic plants from the Mascarene Islands based on their endemism, their medicinal use and their registration in the French Pharmacopeia to evaluate the antiplasmodial, anti-chikungunya and antioxidant activities. The list of these 64 plants including their local name, population, data of collection and voucher number are available in the Supporting Information section. 40 active extracts have been identified from the 38 species: 22 responded positively to the antiplasmodial activity, 8 to the anti-chikungunya activity and 8 to the antioxidant activity. Six plants demonstrated high antiplasmodial activity (IC < 15 µg/mL): Casearia coriaceae, Monimia rotundifolia, Poupartia borbonica, Psiadia retusa, Vernonia fimbrillifera, and Zanthoxylum heterophyllum; and five showed high anti-chikungunya activity (IC < 20 µg/mL): Aphloia theiformis, Stillingia lineata, Croton mauritianus, Indigofera ammoxylum, and Securinega durissima. Eight plants displayed an important antioxidant activity, with values of ABTS, FRAP or ORAC > 2000 µM of Trolox equivalent per mg/mL of extract: Bertiera borbonica, Erythroxylon laurifolium, Erythroxylon sideroxyloides, Indigofera ammoxylum, Poupartia borbonica, Scolopia heterophylla, Sophora denudata, and Terminalia bentzoe. Some data obtained tend to corroborate with the reported traditional use of the plant, such as Zanthoxylum heterophyllum (antiplasmodial), Aphloia theiformis (anti-chikungunya), and Erythroxylon laurifolium (antioxidant).