This meta-analysis was conducted to summarize the comparative effect of NAC and Vitamin E on oxidative status, including total antioxidant capacity (TAC), total oxidative stress (TOS), oxidative stress index (OSI), and hemoglobin (Hb) in patients with TDT.All methods were performed in accordance with the PRISMA checklist. We searched databases including Web of Science (ISI), Scopus, PubMed, and Embase. Meta-analysis was done using Stata statistical software version 16.0.Finally,four randomized-controlled trials (RCT)for NAC and four RCTs for Vitamin E were included.Our meta-analyses showed a significant increase in the weighted mean differences (WMD) of Hband a significant decrease in the WMD of OSI in the NAC group.In subgroup analysis based on age: in the NAC group, a significant increase in the WMD of TAC andHband a significant decrease in the WMD of TOS were detectedonly in children. In theVitamin E group, a significant increase in Hb and a significantdecrease in TOS and OSI were determined in the children subgroup as well.NAC can be used as an effective antioxidant supplementparticularlyin children with TDT. Also, Vitamin Eshowed a beneficial antioxidant effect in TDT children. So, more well-designed randomized, controlled trials for the effect of NAC in adult TDT andthe effect of vitamin E both in adults and children are recommended with more focus on theessential influencing factors on the oxidative status in TDT patients.