Background: Ehretia cymosa Thonn. is a popular medicinal plant used in different parts of West Africa for the treatment of various ailments including diabetes mellitus. Objective: The current study investigates bioactive constituents and in vitro antioxidant and antidiabetic potentials of fractions from extract of E. cymosa. Materials and Methods: Phytochemical investigation and antioxidant assays were carried out using standard procedures. Antidiabetic potential was assessed by evaluating the inhibitory effects of the fractions on the activities of α -amylase and α -glucosidase, while bioactive constituent's identification was carried out using gas chromatography-mass spectrometric (GC-MS) analysis. Results: The phytochemistry tests of the fractions revealed the presence of tannins, phenols, flavonoids, steroids, terpene, alkaloid, and cardiac glycosides. Methanol fraction shows higher phenolic (27.44 mg gallic acid/g) and flavonoid (235.31 mg quercetin/g) contents, while ethyl acetate fraction revealed higher proanthocyanidins (28.31 mg catechin/g). Methanol fraction displayed higher (P < 0.05) 1,1-diphenyl-2-picryl-hydrazyl (0.47 mg/mL), 2,2-azino-bis (3-ethylbenzothiazoline)-6-sulfonic acid (0.49 mg/mL), and hydroxyl radical (0.55 mg/mL) scavenging activities, while ethyl acetate exhibited strong metal chelating (0.61 mg/mL) and superoxide anion (1.68 mg/mL) scavenging activity. Methanol and ethyl acetate fractions displayed higher inhibition (P < 0.05) against α -glucosidase (0.60 mg/mL) and α -amylase (2.11 mg/mL), respectively. Methanol fraction also inhibited α -amylase and α -glucosidase in competitive and noncompetitive modes, respectively. The GC-MS chromatogram of the methanol fraction revealed 24 compounds, which include phytol (1.78%), stearic acid (1.02%), and 2-hexadecyloxirane (34.18%), which are known antidiabetic and antioxidant agents. Conclusion: The results indicate E. cymosa leaves as source of active phytochemicals with therapeutic potentials in the management of diabetes.