HbE-beta thalassemia is caused by an interaction between HbE and defective β gtobin gene of thalassemia. Repeated blood transfusions cause an iron overload, triggering an enhanced generation of free radicals. In the present study, the anti-oxidant property of ethanolic extract of the leaves of Piper betle Linn. (PB) was evaluated in the erythrocytes from patients with HbE-beta thalassemia. In patients with HbE-beta thalassemia (n = 30) and age- and sex-matched healthy individuals (n = 30), the baseline level of reactive oxygen species (ROS) and free radical scavenging activity in the erythrocytes was measured by flow cytometry using dihydrodichlorofluorescein diacetate (H 2 DCFDA), in terms of the geometric mean fluorescence channel (GMFC). The baseline generation of ROS was significantly higher in the erythrocytes from patients with HbE-beta thalassemia, as compared to healthy volunteers, the GMFC being 67.20 ± 4.64 vs. 23.03 ± 1.88 (p<0.001), which was effectively decreased by PB. Similarly, H 2 O 2 (0.5-1.0 mM) induced a higher increase in the GMFC in the erythrocytes from patients with HbE-beta thalassemia, as compared to controls which was effectively reduced by PB. Taken together, PB showed promising anti-oxidant activity against the erythrocytes from patients with HbE-beta thalassemia.