Thrombosis, the development of blood clots in the circulatory system, presents a notable global health challenge. Encouragingly, natural sources derived from annelids, such as lumbrokinase found in earthworms and hirudin from leeches, and demonstrate potential as antithrombotic compounds. In this study, the modified fibrin plate method was employed to reveal the substantial specific fibrinolytic activity of 816 U/mg in Eisenia fetida. This was estimated from a standard fibrinolytic activity curve, demonstrating dose and time-dependent blood clot lysis activity in an in-vitro model. Incubating crude earthworm tissue extract at concentrations ranging from 0.055mg to 0.22mg resulted in clot lyses percentages of approximate 50.00% and 70.00% after 180 minutes. Historically esteemed for its medicinal value, the leech, Hirudo medicinalis, demonstrated notable efficacy in preventing blood clot formation compared to heparin in our investigation. We observed a significant APTT prolongation to 50 seconds, exceeding the normal range of 25 to 35 seconds, prompting an exploration of hemostatic disruptions. Furthermore, a dose-dependent relationship with medicinal leech tissue extract showed a systematic delay in blood clot formation. Hirudin activity, assessed through the thrombin titration method, revealed a specific activity of 13,000 ATU/mg. This comprehensive study underscores the medicinal significance of annelids, like earthworms and leeches as thrombolytic and anticoagulant agents in traditional medicine. Their accessibility, affordability, and minimal side effects further highlight their potential in addressing thrombosis-related disease.