Penyakit kardiovaskular merupakan salah satu penyebab kematian tertinggi di dunia. Penggunaan obat antikoagulan dan enzim fibrinolitik efektif dalam mengobati penyakit kardiovaskular, tetapi menimbulkan efek samping bagi kesehatan dan tergolong mahal. Oleh karena itu, perlu adanya studi mengenai agen fibrinolitikyang lebih murah, aman dan efektif.Carica papayaL. adalah tanaman berbuah yang banyak dikultivasi di daerah tropis termasuk Indonesia. DaunC. papayamengandung empat protease sistein yang berkontribusi sebesar 69-89% dari total protein secara keseluruhan. Salah satu protease sistein yang diduga memilikikemampuan fibrinolitik adalah Papain. Oleh karena itu, dilakukan studi lebih lanjut terkait potensi daun C. papaya sebagai agen fibrinolitik baik secara in-vitromaupun in-silico. Dalam penelitian ini, dilakukan uji degradasi gumpalan darah, danfibrin plate assayuntuk mengevaluasi aktivitas Fibrinolitik secarain-vitro. Hasil menunjukkan bahwa daunC. papayaberhasil mendegradasi fibrin secaralangsung. Untuk mengevaluasi mekanisme katalitik dari Papain, maka dilakukan prediksi situs pemotongan rantai fibrin dan studimolecular docking secara in-silico. Papain terbukti dapat memotong ketiga rantai fibrin yaitu rantai , , dan . Dalam simulasimolecular docking, diketahui bahwa residu katalitik Cys25 dan His159 berperanpenting dalam proses katalitik yang menyebabkan pemotongan ikatan peptida dari kompleks protein fibrin. / Cardiovascular disease is one of the highest causes of death in the world. The use of anticoagulant drugs and fibrinolytic enzymes is effective in treating cardiovascular disease, but causes side effects for health and is quite expensive. Therefore, there needs to be a study of fibrinolytic agents that are cheaper, safer and effective. Carica papaya L. is a fruiting plant that is widely cultivated in tropical regions including Indonesia. C. papaya leaves contain four cysteine proteases that contribute 69-89% of the total protein. One of the cysteine proteases thought to have fibrinolytic abilities is Papain. Therefore, further studies were conducted regarding the potential of C. papaya leaves as fibrinolytic agents both in-vitro and in-silico. In this study, blood clot degradation tests, and fibrin plate assay were conducted to evaluate fibrinolytic activity in-vitro. The results showed that C. papaya leaves successfully degraded fibrin directly. To evaluate the catalytic mechanism of Papain, predictions of fibrin chain cleavage sites and molecular docking studies were carried out in-silico. Papain proved to be able to cut all three fibrin chains namely α, β, and γ chains. In molecular docking simulations, it is known that catalytic residues Cys25 and His159 play an important role in the catalytic process that causes the cleavage of peptide bonds from the fibrin protein complex.