Collagenases and nattokinase are two distinct enzymes with significant therapeutic applications. Collagenases, a family of enzymes that break down collagen, are crucial for normal development, wound healing, and tissue regeneration. They are a broad family of proteins that make up approximately 30% of total protein composition and are a major protein in the extracellular matrix. Collagenases are used to treat conditions such as Peyronie’s disease, wounds, burns, and glaucoma, as they can break down excess or abnormal collagen. Plant-derived collagenases are less utilized compared to microbial ones due to the complexity of plant systems. Nattokinase is a serine protease from fermented soybeans that exhibits powerful fibrinolytic (clot-dissolving) properties. It directly hydrolyzes fibrin and enhances the body’s natural fibrinolytic activity by converting prourokinase to urokinase and elevating tissue plasminogen activator (t-PA) levels. Unlike conventional agents, nattokinase has minimal side effects and can be absorbed orally. Its therapeutic uses include reducing nasal polyps in chronic rhinosinusitis, potentially degrading the SARS-CoV-2 spike protein, and demonstrating antitumor effects by modulating the tumor microenvironment. It also has protective effects against retinopathy and exhibits antiplatelet and antithrombotic properties.