Conclusions: our results show that hesperidin treatment improved GH-induced oxidative stress and mitochondrial dysfunction, in part by suppressing DNMT1-mediated miR-149 silencing. Hesperidin reduced insulin resistance by increasing GH-induced oxidative stress and mitochondrial dysfunction through miR-149 reduction. Mechanistically, hesperidin treatment increased miR-149 expression levels by reducing its promoter methylation through DNMT1 inhibition. BACKGROUND: Hesperidin, a natural flavanone, has been shown to have several protective effects in diabetic rats, including antioxidant, anti-inflammatory and anti-apoptotic effects. Before starting any natural, integrative, or conventional treatment, it is advisable to seek the advice of a qualified physician. It is important to note that deletion of miR-149 apparently nullified the biological functions of hesperidin. By providing the information contained herein, we are not diagnosing, treating, curing, mitigating, or preventing any disease or medical condition. However, the molecular mechanisms underlying the action of hesperidin are not well understood. Over 500 pages of information and alternatives to natural medicine.