The research on the application of enzyme drugs has become a hot spot in the field of biopharmaceuticals. Increasing number of enzymatic drugs have contained in pharmacopoeias in various countries, and most of them have become effective treatment drugs for various major diseases. Enzymes have great affinity and specificity for substrates and can catalyze the transformation of a variety of target molecules into desired products that make enzymes as special and effective drugs and perform therapeutic biochemical reactions, which can’t be performed by small molecules. Utilizing biotechnology to promote the development of new enzymatic drugs, and chemical modification to reduce the immune prototype of therapeutic enzymes and improve their relative stability are the current research direction of exploring enzymatic drugs. This review systematically summarizes the latest research progress and prospects of enzymes as therapeutic drugs at home and abroad.