Objective: It is well known that increased oxidative stress leads to tissue damage in beta-thalassemia (beta-thal) patients. Thiols are one of the most important antioxidant agents, and thiol/disulfide (SH/SS) homeostasis is a novel oxidative stress marker. This study aimed to investigate the relationship of thiol levels, SH/SS homeostasis, and ischemia-modified albumin (IMA) in patients with beta-thal. Materials and Methods: A hundred transfusion-dependent beta-thal patients and 41 healthy controls were included in the study. Results: Native thiol, total thiol, disulfide, catalase, and IMA levels were significantly higher in the beta-thal group compared with the control group (P<0.02). There were no correlation between serum ferritin level and SH/SS homeostasis, and weak positive correlations were found between serum ferritin and IMA (r=0.242, P=0.022). Conclusions: Our study results suggest that antioxidant systems try to compensate for peroxidative damage in the patients' group and serum IMA level was found increased because of increased oxidative status. To the best of our knowledge, there has been no report evaluating plasma dynamic SH/SS homeostasis in beta-thal patients.