The study investigated the moderating role of Grapefruit Seed Extract (GSE) on Epidoxorubicin (EPI)-induced testicular injury. Thirty rats weighing 200-250 g were divided into three treatment groups A, B and C. Group A (Control) received a single dose intraperitoneal injection of 1 mL physiological saline following treatment with 0.5 mL peanut oil (vehicle) for 2 weeks. Groups B and C each received a single dose intraperitoneally of 10 mg kg-1 body weight EPI following 2 weeks gavage administration of 10 mg kg-1 body weight ethanol extract of grapefruit seed and 0.5 mL peanut oil respectively. All animals were sacrificed 4 days after EPI or physiological saline injections by decapitation. Results showed that GSE attenuated testicular weight loss resulting from EPI treatment. EPI-induced reduction in sperm motility and epididymal sperm concentration as well as increase in total abnormal sperm rates were all normalized in the group pretreated with GSE. Similarly histopathological changes in the testis following EPI administration were effectively reverted by GSE pretreatment. Testicular lipid peroxidation as reflected by malondialdehyde level was significantly more in group C than group B (p< 0.05). Lipid peroxidation in Group B was higher but not significantly different from the control. There was however no significant difference in the plasma testosterone levels in all the groups. We conclude that pretreatment with grapefruit seed extract may attenuate epidoxorubicin-induced testicular toxicity.