**Abstract**

Protein and peptide-based drugs have great potential applications as therapeutic agents since they have higher efficacy and lower toxicity than chemical drugs. However, difficulty with their delivery has limited their use. In particular, their oral bioavailability is very low, and the transdermal delivery faces absorption limitations. Therefore, most of the protein and peptide-based drugs are administered by the parenteral route. However, this route also has some problems, such as patient discomfort, especially for pediatric use. Extensive research has been performed over the past few decades to develop protein and peptide delivery systems that circumvent the problems mentioned above. Various strategies that have been employed during this time include nanoparticle carriers, absorption enhancers, enzyme inhibitors, mucoadhesive polymers, and chemical modification of protein or peptide structures. However, most of these strategies are focused on the delivery of proteins or peptides via the oral route since it is the most preferred route considering its high level of patient acceptance, long-term compliance, and simplicity. However, other routes of administration such as transdermal, nasal, pulmonary can also be attractive alternatives for protein and peptide delivery. This chapter will discuss the most effective approaches used to develop protein and peptide drug delivery systems.

**Keywords:** bioavailability, liposomes, nanoparticle carriers, absorption enhancers, enzyme inhibitors, mucoadhesive polymers, chemical modification, aquasome, iontophoresis, electroporation, sonophoresis, transfersomes
