Biomacromolecules play an important role in the treatment of many diseases, but their topical application has been limited by their poor cell membrane permeability. Cell-penetrating peptides (CPPs) have been investigated over the past few decades as a potential strategy to overcome this challenge. CPPs can effectively mediate the cellular uptake of poorly internalized biomacromolecules without unfavorable side effects and have therefore attracted considerable interest as a viable alternative to existing parenteral therapies involving biomacromolecules. In this review, we will highlight the application of CPPs to the non-invasive delivery of biomacromolecules, with a focus on percutaneous and nasal absorption of biomacromolecules administered using CPPs.