Followed by developing modern medicine, leeches did not have extensive use as before, however, in the late 19th century, they were still used in most countries all over the world. Thus far, leeches were utilized in treating various diseases like skin disorders, arthritis, and cancer. In Egypt, using leeches for treatment dates back to early 1500 BC. A medical leech’s salivary glands involve over 100 bioactive materials and the salivary gland secretion contains bacteriostatic, analgesic, and anti-coagulation influences; with resolving activity, it causes microcirculation disorders elimination, restoring the hurt vascular permeability of organs and tissues, removing hypoxia, decreasing blood pressure, increasing immune system activity, and detoxifying the organism by antioxidant paths. The current work reviews the innovative treatment with medical leech especially proteins in leech saliva with high potential in medicine. The results showed that by the virtue of salivary gland secretions which are proteinaceous enzymes, leech acts on various diseases such as venous congestion in reconstructive and plastic surgery, osteoarthritis, cardiovascular diseases caused by blood coagulation disorders, skin disorders, migraine headache, diabetic foot ulcers, priapism, macroglossia, cancer complications, wounds and many other. To confirm the potential therapeutic impacts of leech treatment, more studies are required in more extensive areas with more exact methodologies.