Seaweed-derived heparin-like substances such as fucoidan have been extensively studied in vitro as potential blood anticoagulants. However, there have been no human studies investigating the anticoagulant activity of fucoidan when administered orally. This pilot clinical trial was aimed to assess the safety and clinical effects of fucoidan ingestion on hemostasis as well as study its in-vitro anticoagulant activity. In a single-blinded clinical trial, a total of 20 human volunteers were allocated to both the placebo group (n = 10) who ingested 3 g of guar gum capsules and to the active treatment group (n = 10) who ingested 3 g of 75% fucoidan capsules for 12 days. Platelet indices, activated partial thromboplastin time, antithrombin-III, thrombin time, prothrombin time, and antifactor-Xa were analyzed according to standard methods. In vivo, activated partial thromboplastin time increased from 28.41 to 34.01 s (n = 10, P = 0.01), thrombin time decreased from 18.62 to 17.55 s (n = 10, P = 0.04), and antithrombin-III increased from 113.5 to 117% (n = 10, P = 0.03). The in-vitro fucoidan anticoagulant activity was found prominent. It increased activated partial thromboplastin time, thrombin time, and prothrombin time, whereas antithrombin-III decreased. In-vivo effect of fucoidan on hemostasis was not obvious probably due to low intestinal absorption. Thus, fucoidan in the form used in this study does not seem to have an oral anticoagulant activity, but it has a very strong in-vitro anticoagulant activity.