We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate <i>in vitro</i> Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer <i>in vitro</i> Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin <i>in vitro</i> and growth-inhibitory effects of metformin <i>in vitro</i> and <i>in vivo</i><b>Conclusions:</b> Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin.<i></i>.