Objective: Ionizing radiation induces deleterious effects in the biological systems by producing free radicals. Grape Seed Extract (GSE) as a free radical scavenger could protect the body against the damages. Materials and Methods: In this study, 12 healthy male volunteers were divided into Groups 1, 2, 3 and 4 and received 100, 300, 600 and 1000 mg GSE, respectively. Peripheral blood samples were collected from each volunteer 15 min before, and 1, 2, and 5 hr after GSE oral administration. Blood samples were then irradiated with 150 cGy of 100 kvp X-ray (Irradiated control group, was treated with only 1. 5 Gy of X-rays). Cytogenic damages were detected by micronucleus assay. Results: Results showed that irradiation significantly increased the incidence of micronuclei (p<0. 001). In group 1, the mean reduction of micronucleus rate was 26. 53%, 34. 92%, and 31. 38%, 1, 2, and 5 hr after GSE ingestion (p<0. 001), respectively; this variable in group 2 was 17. 38, 38. 33, and 31. 38 (p<0. 001), in group 3, was 35. 65%, 46%, and 37. 15% (p<0. 001), respectively and in group 4, was 41. 35%, 51. 73%, and 50. 55% (p<0. 0001), respectively. The samples collected 1, 2, and 5 hr after ingestion of GSE exhibited a significant decrease in the incidence of micronuclei compared with the radiation control group. The maximum protection and reduction in frequency of micronuclei (51. 73%) was observed 2 hr after ingestion of 1000 mg GSE. Conclusion: Consumption of GSE before undergoing radiation protects human lymphocytes against X-rays by reducing radiation-induced genotoxicity.