Due to advancements in the field of biotechnology, a plethora of therapeutic proteins and peptides are being produced on a commercial basis. This chapter highlights the intestinal mucosal barriers which prevent peptide and protein absorption and the novel polysaccharide-based nanotechnologies for overcoming the hurdles in absorption of peptide drugs. Peptides are found to be more effective than antibodies due to their smaller size, which permits superior penetration into the tumor with excellent biocompatibility. Polysaccharide-based delivery systems have recently emerged as one of the most widely investigated natural polymers in the nanomedicine domain. Polysaccharides are the natural polymers that have proven to be an attractive substitute for the synthetic polymers in designing nanoparticulate delivery systems for oral protein and peptide delivery. The overall aim of polysaccharide-based nanocarrier systems is to improve the protein bioavailability in vivo and also to improve the residence time.