Monoclonal antibodies are biotherapeutics and one of the distinguished class of medicines which are being extensively used for the treatment of life-threatening diseases such as cancer and various infectious diseases. However, their formulations are challenging due to the complex structure of those protein-type therapeutics. mAbs are administered via injections either intravenous (IV), infusion route (need hospitalization) for high bioavailability and rapid action, or subcutaneous (SC) route (self-administration by patients using specialized SC injection pens), or intravitreally for very few mAbs. The injection route is not convenient for patients. Therefore, pharmaceutical industries and scientists are trying to find an alternative for this painful injectable route via noninvasive routes like oral, transdermal, and inhalation routes. Consequently, novel delivery systems have been explored to optimize the final products of mAbs—to be adaptable by these novel routes—through either formulations' technology or fabrication of the mAb delivery systems. Therefore, this chapter will discuss various novel approaches (e.g., drying technologies and particulate systems) to solve challenges in achieving effective mAb delivery via noninvasive routes (more specifically oral, transdermal, and inhalation routes of drug administrations).