Controlling platelet activation and clotting initiated by cardiovascular interventions remains a major challenge in clinical practice. In this work, the antithrombotic properties of a polysaccharide-based nitric oxide (NO)-releasing dextran derivative are presented. Total platelet adhesion, platelet morphology and whole blood clotting kinetics were used as indicators to evaluate the anticlotting properties of this material. With a total NO delivery of 0.203 ± 0.003 μmol, the NO-releasing dextran derivative (Dex–SNO) mixed with blood plasma demonstrated a significantly lower amount of platelet adhesion and activation onto a surface and reduced whole blood clotting kinetics. Nearly 75% reduction in platelet adhesion and a significant retention of platelet morphology were observed with blood plasma treated with Dex–SNO, suggesting this to be a potential antiplatelet therapeutic agent for preventing thrombosis that does not have an adverse effect on circulating platelets.