Hemorrhage, a common consequence of diseases, surgical procedures, and traffic accidents, poses a significant threat to public health. Effective hemostasis is crucial for patient survival and prognosis, particular in case of internal bleeding. While polysaccharide microsphere-based hemostatic materials have gained clinical acceptance due to their effectiveness, good biocompatibility, and versatility in both intravascular and extravascular hemostasis, they are limited by their single function and insufficient hemostatic properties. Recently, booming developments have been witnessed in microsphere-based biomaterials to achieve a combination therapy for hemostasis. This review first examines the fundamentals of coagulation process, hemostatic mechanisms, and microsphere fabrication techniques. We then discuss the latest investigations in functionalized microsphere-based hemostatic materials for controlling intravascular and extravascular hemorrhage, focusing on design strategies, hemostatic properties, and clinical implementation. Finally, we also propose some limitations and challenges of these hemostatic materials, aiming to provide valuable insights for future research in novel polysaccharide microsphere-based biomaterial.