Background: Thrombosis represents as the prime contributor to the burden of diseases, worldwide. Conventional anticoagulants for thrombosis therapy have a common bleeding side effect. Bioactive peptides are studied to be an effective alternative for currently available therapeutic drugs. Objective: In this study, VITPOR AI peptide, a previously reported coagulation FXIIa inhibitor from Nori (Porphyra yezoensis), was assessed for its inhibitory activity against FXIIa and its in vivo mode of action. Methods: In vivo efficacy as well as the antithrombotic property of the peptide was evaluated in mice model by ex vivo activated Partial Thromboplastin Time assay, tail transection model and whole blood clotting time. The enzyme kinetics was studied using chromogenic substrate assay. Results: The kinetic behaviour of VITPOR AI showed that the peptide is a competitive inhibitor of FXIIa. Peptide showed significant inhibition of platelet adhesion and aggregation. VITPOR AI exhibited significant antithrombotic activity. Furthermore, ex vivo activated Partial Thromboplastin Time assay revealed that VITPOR AI exhibited potent anticoagulant activity in vivo. Tail bleeding assay revealed that the peptide did not prolong bleeding time in mice even at a higher dose of 5 mg/kg. Cytotoxicity studies of the peptide against human blood leukocytes indicated the safety of the peptide. Conclusion: VITPOR AI could be prospected as a potent anticoagulant with Factor XIIa inhibition, antiplatelet aggregation and antithrombotic activity. It was also studied to have no bleeding side effect. © 2020 Bentham Science Publishers.