This review was performed to determine the potential of drugs that can remove or decrease the requirements for blood transfusion among beta (β)-thalassemia patients. A comprehensive literature search was conducted to identify clinical trials and studies using PubMed Central, Google Scholar, PubMed, and ScienceDirect archived articles published from 1996 to November 2023. According to this review, clinical trials for a number of drugs, including luspatercept, sotatercept, mitapivat, etavopivat, hydroxyurea, rapamycin, decitabine, thalidomide, and quercetin, have been performed as part of efforts to improve the cure strategy for β-thalassemia. Of these drugs, luspatercept and sotatercept have exhibited particularly promising results and have been granted US Food and Drug Administration (FDA) approval for use in β-thalassemia patients. The mode of action for the drugs luspatercept and sotatercept involves the stimulation of hemoglobin (Hb) production or enhancement of its functionality, thereby decreasing reliance on blood transfusions and enhancing the overall quality of life. In this way, drugs like luspatercept and sotatercept present an opportunity to notably decrease the necessity for blood transfusions in β-thalassemia patients, improving their standard of living and overall prognosis. However, more research is needed to evaluate the effectiveness and safety of these drugs in the long run.