Background: The effects of low radiation exposures are naturally harmful to the humans and in this study we aimed to investigate the radioprotective effects of Gongronema latifolium extracts (GLE) against radiation induced oxidative stress. Materials and Methods: Forty eight rats were divided into control and experimental groups. The control group had two sub-groups; (i) normal control (NC) was neither irradiated nor treated with GLE and (ii) irradiated control (IC) was irradiated (with 4 and 6 Gy) but no GLE treatment. The experimental group also had two sub-groups; (i) pre-treated (PRT) was treated with GLE before irradiation and (ii) post-treated (PST) was irradiated before treatment with GLE. Radioprotective effects were measured by noting changes in biochemical parameters of liver, lipid peroxidation, antioxidants enzymes and changes in body weight that occurred in the sub-groups. ANOVA with Tukey’s test were used to determine significance differences in the sub-groups. Results: There were significant changes in all biochemical enzyme markers between the NC and IC with values of % inhibition of lipid peroxidation 33±1.5 and 71 ± 5.5 at 6 Gy dose of radiation exposure. The values of lipid peroxidation in PRT and PST differed significantly from the IC with values 35 ± 5.0 and 57 ± 1.0 at 6 Gy respectively; thus significant difference exists between PRT and PST. The IC sub-group recorded the highest radiation induced weight loss (56%). Conclusion: Preliminary result indicates that GLE ameliorated oxidative stress in pretreated sub-groups than in post-treated sub-groups, suggesting GLE as a potential prophylaxis.