Poly (lactic-co-glycolic acid) (PLGA) is used to prepare biocompatible and biodegradable nanoparticles (NPs). Unfortunately, PLGA NPs suffer from certain limitations such as short residence time when applied on mucosal tissues. Coating PLGA NPs surfaces with chitosan can improve their mucoadhesiveness and enhance the residence time. In this study, two molecular weights of chitosan (60 and 15 kDa) and three degrees of deacetylations (DDA) (92%, 75% and 55%) were used to study the effect of the molecular weight, concentration, and DDA of chitosan on the properties (size, PDI, charge, and mucoadhesion) of PLGA NPs. The results showed that the size of the NPs increases with increase in the concentration or molecular weight of chitosan but decreases with increase in the DDA. Also, coating PLGA NPs with chitosan give them a positive charge that increases as the chitosan concentration, DDA, or molecular weight increase. In general, all formulations with chitosan-coated PLGA NPs had enhanced mucoadhesion, and this mucoadhesion improved as the chitosan concentration, DDA, or molecular weight increased.