Telfairia occidentalis belongs to the family cucurbitaceae. It is a plant with dark green leaves that also bears a pod containing edible seeds. It is widely cultivated in Western Africa, having high commercial importance in the eastern part of Nigeria. It is primarily used in the preparation of soup in the form of vegetable and in herbal medicines for production of blood tonic for weak and ill person, and also for the treatment of other ailments. Telfairia occidentalis leaves extract and fractions were evaluated for its phytochemical constituents, antioxidant activities and GC-MS analysis on the active extract and fractions to identify the bioactive compounds conferring these activities using standard procedures. The phytochemical screening of the ethanol extract and different fractions revealed the presence of flavonoids, alkaloids, tannins, saponin, cardiac glycoside and anthraquinones. The antioxidant activity was carried out using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) model; among the fractions ethyl acetate fraction (84.91%;100 µg/mL) demonstrated the best antioxidant activities in DPPH assay followed by the extract (80%;100 µg/mL), dichloromethane(79.51%;100 µg/mL) and n-hexane fractions (46.63%;100 µg/mL) with IC50 of 22.56 µg/mL, 37.43 µg/mL, 37.59 µg/mL, and 91.11 µg/mL. Ferric reducing antioxidant power (FRAP) recorded highest activity at 100 µg/mL with ethyl acetate having the highest antioxidant effect (1.574 nm) compared to ascorbic acid (1.750 nm; 100 µg/mL) followed by DCM fraction (1.040 nm), crude extract (0.966 nm), and n-hexane fraction (0.724 nm). The GC-MS analysis recorded a total of 39 compounds from extract; 9 major constituents; oleic acid, (10.27%), acetic acid (9.66%), hexanoic acid (7.66%), phytol acetate (7.22%), 18,19-seccoyohimban-19-oic acid (6.69%), iso-propyl 9,12,15-octadecatrienoate(6.20%), n-hexadecanoic acid, methyl ester (5.83%), trans-geranyl geraniol (4.21%) and 9,12- octadecadienoic acid (4.11%),39 compounds from DCM with 8 major constituents; (1,1-bicyclopropyl)-2-octanoic acid (25.87%), quinic acid (9%), acetic acid (6.66 %), 9-octadecadienoic acid (z,z) (5.63 %), benzofuran (5.34%), oxirane (4.11%), phytol, acetate (2.52 %) and vitamin E (2.37%), and 37 compounds from ethyl acetate fraction with 7 major constituents; stigmasterol (17.09%), vitamin E (14.73%), stigmasterol (11.25%), 4,22-stigmastadiene-3-one (9.40%), 7,22-ergostadienol (5.84%), dotricontane (3.88%) and eicosane (3.07%). From these results T. occidentalis extract and fractions shows high antioxidant activity. These compounds present in T. occidentalis extract and fractions could provide a rationale for the ethnomedicinal use of the plant in the management of several pathological conditions associated with oxidative stress including type 2 diabetes and inflammatory conditions.