Because of the side-effects of commonly used anti-platelet and anticoagulant drugs, investigations into plant substances with similar activities are very common. Based on our own studies in recent years, we estimate that it is possible to use natural compounds to both inhibit coagulation pathway enzymes and to reduce blood platelets’ activation. As such, in our current study we wanted to verify the anti-platelet and anticoagulant properties of grape seed extract (GSE) using in vitro models. During our analysis, the following parameters were analyzed: Coagulation times, thromboelastometry assays (coagulation time, clot formation time and maximum clot firmness), aggregation of platelets and phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Adenosine diphosphate (ADP)-induced aggregation was lower in GSE 7.5 µg/mL as well as in GSE 15.0 µg/mL. A similar dependence was observed in VASP assays for GSE 7.5 µg/mL and GSE 15 µg/mL. The effect on plasma coagulation tests was distinct only with GSE 15 µg/mL. All of the thromboelastometry variables were statistically significant with 15.0 µg/mL GSE concentration. Our results show, for the first time, the multi-potential effect of grape seed extract on coagulation systems, and clearly suggest that grape seed extract could be considered a promising nutraceutical in the prevention of cardiovascular thrombotic events caused by different mechanisms.