Plasminogen activator inhibitor 1 (PAI-1) stabilizes the thrombus by suppressing the activation of plasminogen to plasmin at the site where the thrombus is formed, thereby inhibiting fibrinolytic reaction. Because inhibition of PAI-1 production or activity facilitates fibrin degradation and eliminates unnecessary thrombus, it is believed that suppression of PAI-1 production or activity prevent thrombosis. Some natural substances that inhibit PAI-1 production and activity were found from medicinal plants, health foods, and purified natural substances and they have potential for realistic use in clinical field or as functional foods. Here, we reviewed these natural products that inhibit PAI-1 production and activity. In addition, we described the potential applications of these substances in clinical field or as functional foods.