In this study, amoxicillin (AMX) loaded into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) were successfully prepared by double emulsion technique using polaxamer 188 as a nonionic surfactant. The prepared nanoparticles (NPs) were successfully coated with different molecular weights of chitosan (CS). AMX-loaded PLGA NPs were coated with CS in order to obtain controlled drug release and increase the bioavailability of AMX. The range of PLGANPs' entrapment efficiency (EE%) was determined to be between 74.39% and 85.63%. EE% showed a definite increase with increasing CS molecular weight. While TEM images revealed that the produced nanoparticles have a spherical form, CS-PLGANPs showed particles that were monodisperse and in the nanosize range. The zeta potential is changing from negative to positive. DSC, XRD, and FTIR confirmed AMX was fully encapsulated in PLGANPs and coated with CS. In vitro AMX release from CS-PLGANPs showed sustained release, although slower release was observed when using CS with a higher molecular weight. According to research on drug release kinetics, CS-PLGANPs released AMX in a diffusion-controlled manner.