Oral drug delivery is and probably always will be patients route of choice. Unfortunately, many high potent drugs show low permeability or rapid degradation when administered via the gastrointestinal tract. Therefore, novel drug delivery systems for better targeting and protection of the drug are on demand. Hence, the aim of this thesis was to improve existing and evaluate novel strategies for oral application. Thereby two different attempts were persuaded, mucoadhesive and mucus penetrating drug delivery systems. For the development of mucoadhesive drug delivery systems different polymers with carbohydrate or poly(acrylic acid) backbones were thiolated as thiol groups show strong interactions with mucus substructures. To overcome drawbacks of free thiolgroups like oxidation and pH depended reactivity, polymers were further modified by attachment of an aromatic mercaptane via disulfide bond formation. These modification led to a more pronounced mucoadhesive effect and to higher reactivity in acidic environment. Additionally, obtained polymers showed strongly improved water-uptake, controlledrelease, a higher viscosity and cohesive properties as a result of a disulfide crosslinking process stabilizing the polymeric matrix. Moreover, mucus penetrating properties of a self-nanoemulsifying drug delivery system (SNEDDS) were improved by using novel C8- and C12-thiols, as the thiol groups are able to break disulfide-linkage of mucus glycoproteins. Further, a protective effect against enzymatic degradation of the SNEDDS for peptide and DNA drugs could be proven in vitro. An in vivo study carried out confirmed improved oral bioavailability of a peptide drug after incorporating into SNEDDS compared to the peptide control solution. Additionally, mucus penetrating nanoparticles were prepared by complex-formation with the mucolytic enzyme papain. The attached enzyme lowers the viscosity of the mucus gel leading to an improved penetration of an incorporated model drug. Regarding results of this thesis, both strategies,mucoadhesion as well as mucus penetration are promising approaches for oral drug delivery especially for sensitive and low permeability drugs.