We found low-molecular-weight fucoidan (LMF) bound to S100A8/A9 with an equilibrium dissociation constant (KD) of 2.368 × 10−8 M. LMF inhibited S100A8/A9-induced platelet hyperactivity and NET formation in vitro, and ameliorated DVT without significantly perturbing hemostasis in vivo. The gene discussed is S100A8; the disease is deep vein thrombosis.