Protein drugs often require needle-based delivery, such as subcutaneous, intramuscular, and intravenous injection. This causes significant discomfort to patients, especially those who suffer from chronic diseases and require frequent and long-term doses. We are developing technologies that overcome mucosal and epithelial barriers to enable systemic absorption or enhanced penetration of proteins from the mucosal sites, including nasal, sublingual, and eye. Protein drugs are simply mixed with these delivery vehicles and then applied to the mucosal sites via sprays or drops. Potential applications include delivery of insulin for diabetes and monoclonal antibodies for autoimmune diseases and cancers.