The proteins and peptides have been as important agents for therapeutic and diagnosis. Many researchers have used biocompatible functional polymers to develop oral peptides delivery for sustained and controllable to improve bioavailability. However, most macromolecules are sensitive and denatured by low pH and rapid enzymatic degradation through the gastrointestinal tract. Further, the macromolecules are hydrophilic and large molecule size that cause difficulty penetrating through transcellular and paracellular routes into the systemic blood circulation. In our study, to overcome these challenges is to use a multilayers microparticles which involved a liposomal core phase encapsulated peptide drug (liraglutide) and a shell phase (Chitosan) used to increase the carrier residence time in the small intestine. In vitro data showed that the LMS002 formulation with particle size under 25 μm and drug loading above 50 mg/g was formed. Performance of the LMS002 was investigated in vivo by comparing the area under the plasma curve of liraglutide after oral, intravenous or subcutaneous (s.c.) application. The relative pharmacological bioavailability of LMS002 was 14% with i.v. liraglutide as reference, whereas the free liraglutide administered orally showed a bioavailability of only 0.4%. This result provided into the potential of multilayer microparticles as novel carrier for oral peptide delivery.