Fibrinolytic complications such as stroke and peripheral occlusive disease due to vascular occlusion are significant causes of poor prognosis and death. Given the ability of mushroom fibrinolytic enzymes to dissolve blood clots and prevent side effects, their use as a potential thrombolytic therapy has attracted great interest. Serine protease, metalloprotease, and serine metalloprotease are protease enzymes that can affect the fibrinolytic mechanism by dissolving blood clots and increasing blood flow. This systematic review aimed to disclose all information regarding the production, purification, and characterization of fibrinolytic proteases from fungi. Searches were conducted on online media databases, including Google and journal sites (NCBI, PubMed, and others, using the keywords "(Fibrinolytic Enzymes) OR (Fibrinolytic Proteases) AND (Fungi or Mushrooms)" from 2012-2023. This systematic review observed reviews from the purification and characterization steps, indicating the need for attention to the manufacturing process and enzymatic applications. The production of these enzymes by fungi is associated with developments in pharmaceutical applications.