Spirulina and Grape Seed Proanthocyanidin Extract (GSPE) were studied for their potential therapeutic and protective properties in hypothyroidism-induced rats. Six equal groups of forty-eight rats were formed. Group 1is a control and Group 2 (hypothyroidism) received an oral dose of carbimazole (1.8 mg/kg b.wt.) every day. Rats in Group3 (GSPE Protected) got (150/kg b. wt) of GSPE per day for the first 3 weeks, then continued administered with carbimazole for another 3 weeks. Group 4 (carbimazole + GSPE treated): Rats were administered a daily dose of carbimazole (1.8mg/kg b.wt) for 3 weeks, followed by GPSE (150/kg b. wt/day) for another 3 weeks. Group 5 (Spirulina Protected); Rats received Spirulina (300 mg/kg body weight per day) for the first three weeks, then continued with carbimazole for another 3 weeks. Group 6 (Spirulina treated): Rats administered a daily dose of carbimazole for 3 weeks, followed by Spirulina (300/kg b. wt/day) for other 3 weeks. The results collected demonstrated a significant rise in liver Caspase-8 gene expression in the hypothyroidism group along with significant increases in blood TSH, total cholesterol, and triacylglycerols. However, serum T3, T4 levels drastically dropped along with Bcl2 expression in the liver tissue. Treatment and protection of spirulina and GPSE reduced TSH, total cholesterol, triacylglycerols and Caspase-8 with significant upregulation of Bcl-2 and marked decrease in total cholesterol and triacylglycerols concentrations. In conclusion, grape seed extracts and Spirulina platensis had therapeutic potential in hypothyroidism, protect liver damage and mitigate Thyroid disruptors via anti-apoptotic activities.Hypothyroidism GSPE Spirulina Thyroid hormones Apoptosis