The contact between the dialysis membrane and blood can induce oxidative stress (OS) and thrombosis, causing oxidative organ damage and impaired toxin clearance. To date, the selection of anticoagulants has focused on mechanisms inhibiting white, but not red (erythrocytes) thrombus formation. In the present study, polyethersulfone (PES) membranes were modified with the antioxidant drug tiopronin, the physicochemical properties and dialysis performance of the Tio‐PES membranes were evaluated. The effects on erythrocyte thrombosis were evaluated in terms of erythrocyte morphology, prothrombotic properties (adhesion, aggregation, viscosity, sedimentation, and hemolysis), and fibrinogen‐erythrocyte interactions. The regular anticoagulant and antiplatelet properties were also assessed. Superoxide dismutase (SOD), malondialdehyde (MDA), plasma protein, and complement C3a were further determined. Finally, the biosafety of the Tio‐PES membranes was evaluated both in vitro and in vivo. The Tio‐PES membranes exhibited excellent physicochemical properties and improved dialysis performance. We found that the Tio‐PES membranes stabilized erythrocyte morphology, reduced erythrocyte prothrombotic properties, decreased FIB adsorption, and prevented red thrombus formation. In addition, the Tio‐PES membranes exhibited excellent antioxidant properties and showed biosafety in our primary toxicity studies. Thus, Tio‐PES membranes hold promise as novel, safe, and effective dialysis materials for potential clinical application.This article is protected by copyright. All rights reserved