Radioiodine ((131)I) has been widely used for the treatment of patients with thyroid diseases. However, there is a persisting concern about the induction of second tumor and genetic damage after (131)I therapy. The purpose of this study was to investigate the radioprotective effects of Origanum vulgare extract against genotoxicity induced by (131)I in human lymphocytes. Whole blood samples from human volunteers were incubated with origanum extract at doses of 12.5, 25, 50 and 100 μg/mL. After 1 hour of incubation, the lymphocytes were incubated with (131)I (20 μCi/mL) for 1 hour. The lymphocytes were then cultured with a mitogenic stimulant to evaluate micronucleus formation in cytokinesis-blocked binucleated cells. Incubation of lymphocytes with (131)I induced additional genotoxicity and shown by increases in micronuclei (MN) frequency in human lymphocytes. Origanum at three last doses significantly reduced the MN frequency in cultured lymphocytes. The maximum protective effect and the maximum decrease in the frequency of MN were observed at 100 μg/mL of origanum, which caused a reduction of 70% (p<0.0001). Origanum extract also exhibited an excellent and dose-dependent radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl-free radicals. This study has important implications for patients undergoing nuclear medicine procedures. The results indicate a protective role for origanum extract against the genetic damage induced by radiopharmaceutical administration.