This study investigated the influence of polyphenol chemicals from Santolina chamaecyparissus and its fractions (SCE) on antioxidant, anticoagulant, and thrombolytic capacities. Polyphenols were extracted using 85% methanol and partitioned with different solvents. The antioxidant activity of SCE was assessed using OH° and ABTS free radical scavenging assays. Anticoagulant and thrombolytic activities were determined in healthy human volunteers. In silico studies employed molecular docking and ADMET tests to examine the interaction of isolated polyphenols with coagulation protein factor Xa. The EAE fraction exhibited the highest total polyphenol content and demonstrated strong scavenging activity against ABTS and OH° radicals. EAE significantly prolonged clotting times, outperforming the standard Plavix, and showed superior clot lysis compared to standard citrate. Molecular docking analysis revealed that Rutin, apigenin-7-o-neohesperidoside, luteolin 7-glucoside, and Lonicerin had high affinity for Factor Xa, surpassing Plavix. Further investigations are needed to evaluate the potential of EAE as an alternative or adjunct therapeutic option.