Background Serum lipids and glycemic dysregulation are the known characteristics of βthalassemia major (β-TM). Here, we evaluated the association of these disorders with insulin resistance (IR), oxidative stress and serum ferritin values in patients with β-TM. Methods This case-control study was performed in thalassemia unite of Darab Hospital (Darab, Fars province, Iran) from December 2016 to December 2017. Forty-eight patients with β-TM and 33 healthy individuals were enrolled. Serum fasting blood sugar (FBS), insulin, total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), ischemia modified albumin (IMA), and ferritin were measured. The values of HOMA-IR, LDL: TG ratio, atherogenic index (AI), atherogenic index of plasma (AIP), and coronary risk index (CRI) were calculated. ResultsThe level of serum ferritin, IMA, FBS, TG, AIP, LDL: TG ratio, and the prevalence of IR (HOMA-IR < 3.8) were significantly higher while TC, LDL-C, HDL-C, and AI were significantly lower in the patients compared to the control group. In patient with β-TM, serum ferritin revealed to have a positive association with serum insulin, HOMA-IR, AI, and CRI levels while serum IMA showed positive association with TG and AIP and inverse association with hypocholesterolemia. HOMA-IR had positive correlation with HDL levels. Conclusions Oxidative stress and iron overload are predictors of serum glycemic and lipid dysregulation, suggesting possible beneficial effect of antioxidants and efficient iron chelating therapy in reducing the risk of metabolic disorders in βthalassemia.