Background: Ionizing-radiation induces oxidative stress and thyroid toxicity. Thyroid function disorders have a great impact on fertility in both sexes. Materials and Methods: Forty female rats were divided into four groups. Control, Spirulina-treated (300 mg/kg); given orally for 15 days, γ-irradiated; given (5 Gy whole body γ-rays) and Spirulina+irradiated; given Spirulina for 15 days before irradiation. Animals were sacrificed the 3^rd day post-irradiation. The level of the oxidant/antioxidant markers: Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) was evaluated. In addition, caspase-3 activity was measured as apoptotic marker and comet assay to detect DNA-damage. Serum thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) were determined to evaluate the thyroid function alterations. Also, analysis of reproductive hormones; follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P4) was detected.  Results: Whole body γ-irradiation-induced oxidative stress, denoted by significant decreases of antioxidant markers and an increase in MDA content. The activity of caspase-3 was significantly increased and comet assay revealed DNA damage. Also, serum level of TSH was significantly increased, while T3, and T4, significantly decreased in irradiated rats. Moreover, the reproductive hormones showed significant decreases. Spirulina treatment has significantly attenuated oxidative stress in thyroid tissues, decreased caspase-3 activity and ameliorated DNA damage, concomitant with significant amelioration in the levels of thyroid and reproductive hormones. Conclusion: Spirulina may alleviate γ-rays-induced thyroid damage and play a significant role in the regulation of thyroid and reproductive hormones in female rats.