Background: Tissue destruction and many diseases are driven by chronic reactive oxygen species (ROS) accumulation. Thyroid hormones could be able to activate ROS, which represent an important mechanism in pathogenesis of cardiovascular disorder. A potent SIRT1 activator (resveratrol) showed to lower oxidative stress, inflammation, autophagy induction, but its cardioprotective effects in hyperthyroid states were not systematically evaluated, so we aimed to investigate its concurrent protective and molecular mechanisms with hyperthyroid disorder and its benefits on cardiovascular indexes. Methodology: 24 adults male wister albino rats (180-200 gm) were equally distributed into; control, resveratrol administrated group, experimentally-induced hyperthyroid group and resveratrol-administrated hyperthyroid group (L-thyroxin + resveratrol through oral gavage for 4weeks). Body weight, heart rate (HR), blood pressure (BP), norepinephrine vascular reactivity and % of upsurge in mean value of arterial blood pressure (ABP) measurements and cardiac hypertrophy index (CHI) were estimated. Blood samples were withdrawn for examinations. After scarification, fresh cardiac and aortic specimens were collected for biochemical, gene expression and histological examination. Results: Statistically significant improvements were observed in the resveratrol-treated hyperthyroid group compared to the untreated hyperthyroid group in terms of heart rate (HR), blood pressure (BP), norepinephrine-induced vascular reactivity, and the percentage increase in the mean arterial blood pressure (ABP) measurements. These improvements were accompanied by restoration of the cardiac health index (CHI), normalization of serum thyroid hormone levels, increased SIRT-1 activity in cardiac tissue, and downregulation of IL-6 and TNF-α gene expression, along with amelioration of histological changes in both heart and aortic tissues. Furthermore, there was a significant reduction in cardiac oxidative stress, inflammation, and fibrotic pathway activation. Conclusion: It is noteworthy that the use of a SIRT1 activator, such as resveratrol, holds significant cardiac and vascular protecting promise in management of hyperthyroid cardiovascular disorder. This effect is achieved through improvements in heart rate (HR), blood pressure (BP), and vascular reactivity, as well as reversal of cardiac alterations involving SIRT1 activity, inflammation, oxidative stress, and fibrotic biomarkers Key words: SIRT 1, IL-6, TNF-α, hyperthyroidism,resveratrol