Flavonoids are a class of naturally occurring plant-derived secondary metabolites with considerable medicinal significance and potential. These polyphenolic phytochemicals are effective against a wide range of diseases and are recognized for their diverse health benefits to humans. Recent research has demonstrated their potential modulatory effects on the biology of the blood hemostasis system, which is a complex system with different sophisticated processes responsible for maintaining normal blood clotting, preventing hemorrhage, ensuring proper blood fluidity, wound healing, and preserving vascular integrity. Malfunctions or hyperactivity in the hemostasis system can lead to various disorders like deep vein thrombosis, myocardial infarction, arterial thrombosis, pulmonary embolism, thrombotic stroke, and coronary artery diseases. Focusing on both in vitro and in vivo and some ex vivo studies, this review highlights how different classes of natural and synthetic flavonoids can act as anticoagulants and antiplatelet agents. Furthermore, this review also explores the underlying mechanisms by which flavonoid phytochemicals interact with the blood hemostasis system and target its various elements. We also provide a concise overview of classification, biosynthesis, and chemical diversity along with a brief outline of various functions of plant flavonoids and their protective effects against multiple diseases in humans. By shedding light on the molecular interactions and pathways modulated by flavonoids acting in the hemostasis system, this review aims to offer valuable insights into their prospective therapeutic use and implications for future research on the modulation of hemostasis and related blood clotting disorders associated with various cardiovascular diseases.