The use of poly(D, L-lactic-co-glycolic acid) for DNA delivery application is limited by its negative surface charge and acidic degradation products. The motivation of the present work was to study the effects of chitosan incorporation into PLGA foams on DNA delivery. PLGA/chitosan composite foams loaded with luciferase plasmid were fabricated by a combination of spray drying and supercritical CO2 foaming techniques. The resultant composite foams showed good morphology and chitosan was found to be poorly crystallized in the PLGA matrixes. The composite foams exhibited a sustained release of DNA (5-9 weeks) with decreasing release rate upon increasing content of chitosan. With this encapsulation technique, it was also observed that the integrity of plasmid was well maintained. Moreover, cell culture results proved that the bioactivity of plasmid released from all foams was well maintained and the incorporation of chitosan in foams helps increase cell adhesion and maintain high cell viability. Therefore, it can be concluded that PLGA/chitosan composite foams fabricated by combining spray drying and supercritical CO2 foaming are promising in DNA delivery applications.