The presence of chromosomal damage in bone marrow cells affected by several diseases such as thyroid, cancer etc., was detected by the micronucleus (MN) assay. The present study was designed to evaluate: i) volatile components of Ulva rigida, ii) effects of hypothyroidism on bone marrow MN frequency, iii) effects of oral administration of Ulva rigida ethanolic extract (URE) on MN frequency produced by hypothyroidism, and iv) thyroid hormone levels in normal and 6-n-Propylthiouracil (PTU)-induced hypothyroid rats. The volatile components of Ulva rigida was studied using a direct thermal desorption (DTD) technique with comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOF/MS). URE administration was of no significant impact on thyroid hormone levels in control group, while PTU administration decreased thyroid hormone levels compared to control group (p < 0.001). Moreover, URE supplementation resulted in a significant decrease in MN frequency in each thyroid group (p < 0.0001). This is the first in vivo study that shows the strong antigenotoxic and protective effect of URE against the genotoxicity produced by hypothyroidism.