Plants continue to constitute key elements of medical practice in West African countries. The Cabo Verde archipelago hosts a great diversity of medicinal plants and local markets are considered important sites for trading plants harvested by rural communities. This study has two main goals: (i) to assess the medicinal uses of native species in Santiago, the biggest island of the archipelago, and (ii) to evaluate the antioxidant, antimicrobial and antidiabetic/antihyperglycemic activities of two native trees (Tamarix senegalensis and Sideroxylon marginatum) used in traditional medicine and traded in local markets. Our results revealed that on Santiago Island, 24 native plants are used in traditional medicine. The main uses of these species (e.g., forage, timber, food and fibres), their medicinal applications, the plant parts used, their mode of administration and conservation status are presented here for the first time. Moreover, the pharmacological characterization of two native tree species revealed that hydroethanolic extracts were richer in phenolic compounds and more active than their aqueous counterparts. All the studied extracts revealed significant antioxidant properties (DPPH and FRAP assays) and were generally moderately active against Gram-positive bacteria. All the extracts inhibited the activities of the carbohydrate digestive enzymes α-glucosidase and α-amylase in a dose-dependent manner. For α-glucosidase, the detected inhibitory activity (IC50 values from 2.0 ± 0.2 μg/mL to 9.9 ± 1.2 μg/mL) was significantly higher than that of acarbose, suggesting that extracts of both species can delay glucose absorption, thereby assisting in slowing down the progression of diabetes. Our findings highlight the crucial importance that medicinal plants have for the Cabo Verdean population, while also raising awareness on the need for sustainable use and conservation of native flora, and of tree species traded in local markets in particular.