Hyper- or Hypothyroidism is an overactive or underactive thyroid gland that prevents the body from operating properly. The potential therapeutic effects of spirulina platensis and GSPE on experimental hypothyroidism and hyperthyroidism in rats were evaluated. A total 96 rats were divided into two main experimental groups: Experiment A: carbimazole-induced hypothyroidism (1.8 mg/kg b. wt.) and experiment B: induced hyperthyroidism (50, 100, 200 μg/kg b. wt.) for the first three weeks, respectively. The administered GSPE dose (150mg /kg b. wt./day) and Spirulina (300 mg/kg b. wt./day) for 3 weeks. The hyperthyroidism experiment (A) six sets of rats were used: Group 1 (control normal), Group 2 (hyperthyroidism), Group 3 (GSPE Protected): GSPE administered for the first 3 weeks and continued with thyroxine for another 3 weeks. Group 4 (GSPE treated): thyroxine administered for 3 weeks, followed by GPSE as in group 3. Group 5 (Spirulina Protected); spirulina and thyroxine administration as in group 3. Group 6 (Spirulina treated): spirulina and thyroxine administration in group IV. The hypothyroidism experiment (B) rats divided also into 6 groups like to the above design in hyperthyroidism experiment (A) but carbimazole dose was stable (1.8 mg/kg b. wt.) in the 3 weeks. In hyperthyroidism spirulina and GPSE significantly increased serum total cholesterol, triacylglycerols with down regulation of liver Caspase-8 and significant upregulation of Bcl2 gene. In hypothyroidism spirulina and GPSE exhibited down regulation in liver miRNA 224, PKCα with significant upregulation of miRNA 382 gene in hypothyroid rats. Spirulina and grape seed may treat and prevent hyperthyroidism or hypothyroidism in rats.