Recent advances in genetic engineering and pharmaceutical biotechnology have made possible to combat life-threatening diseases with efficient delivery of therapeutic proteins. These advancements have increased the significance of therapeutic proteins in pharmaceutical market, but their therapeutic delivery to the targeted site is still a major obstacle to achieve desired therapeutic outcomes. In most cases, majority of the therapeutic proteins are usually administered via oral routes which encounter many problems notably enzymatic degradation, poor solubility and nonlinear pharmacokinetics. Besides this route, many other routes like mucosal, intra-nasal, intra-vaginal, pulmonary and transdermal have also been used for the delivery of therapeutic proteins. In order to keep these therapeutic proteins safe from enzymatic degradation and improve their therapeutic efficacy, several strategies have been designed and investigated various therapeutic delivery routes for efficient delivery of therapeutic proteins to the targeted site with minimal side effects. In this article, we have comprehensively summarized the recent advances and developments that have been adopted for delivery systems of these therapeutic proteins via invasive and/or non-invasive routes.