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Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin \u03b12\u03b21-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a <jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub> of 3.45\u2009\u00b1\u20091.06\u2009\u03bcM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion <jats:italic>in vitro<\/jats:italic> with a reduced <jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub> of 1.83\u2009\u00b1\u20090.29\u2009\u03bcg\/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed <jats:italic>in vivo<\/jats:italic> with a 50% reduction of thrombus weight. 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