Background: Plants are important sources of therapeutic proteases with expressive activity, stability, specificity, and efficiency. These proteases are employed at low concentrations and produce lesser side effects. They have complex tridimensional structures whose maintenance is a challenge, requiring specific conditions to guarantee the biological and pharmacological activities of these compounds. Aims: To conduct a literature review about plant therapeutic proteases, their principal biochemical aspects, potentials and clinical applications, and main pharmaceutical formulations. Materials and Methods: The present study consisted of a bibliographic survey of the major plant therapeutic proteases. An investigation was performed in the PUBMED, SciELO, ScienceDirect and Academic Google databases using the keywords plant enzymes, therapeutic protease, immobilization, formulation. Results: Some plant therapeutic proteases, such as papain and bromelain, are employed to treat many diseases and conditions, but the complexity of their structures is an important limitation of their uses. Thus, the structure and activities of their formulations need to be stabilized and protected against degradation, with improved pharmacokinetics, a prolonged time of action, reduced toxic effects, and proper direction towards their therapeutic target. Nanotechnology has made it possible to manufacture drug carriers such as polymeric nano- and microparticles, hydrogels, dendrimers and liposomes which are able to increase their efficacy and clinical applicability, as well as patient compliance. Sustainability initiatives that use Green Chemistry together with nanobiotechnology have managed to reduce the risks of toxicity to organisms and the environment. Green synthesis uses lower concentrations of metal ions, water-soluble, biocompatible and non-toxic compounds, as well as seeking energy efficiency and using renewable sources of raw materials. Conclusions: Investigations about new formulations of plant therapeutic proteases using biodegradable and biocompatible polymers is of great biomedical interest because they generate less toxic new biopharmaceuticals, in addition to protecting and stabilizing the enzymatic structure.