Various formulation strategies have been investigated for non-invasive delivery of antimicrobials into the oral cavity for the treatment of the oral infections. In general, mucoadhesive polymers have been used to keep the delivery system at the application site for an extended period of time, avoiding the removal of the drug by tongue movement, as well as salivation and swallowing. Chitosan, as a mucoadhesive biopolymer has become a very promising material in development of oral mucosal delivery systems, which can be prepared in various forms such as gels, films, sponges, tablets, micro/nanoparticles. The aim of the present study was to investigate different types of chitosan, with different molecular weight and solubility properties as a delivery system, as well as for its antimicrobial activity against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans strains. For this purpose, gel formulations were prepared using different types of chitosan obtained from animal (crab shell) or non-animal (white mushroom) sources, and chlorhexidine gluconate (Chx), which is widely used in clinical dental practice as an antiseptic oral rinse due to its activity against a wide range of microbial species, was incorporated into the formulations at 0.1 and 0.2% w/v concentrations. Formulations were compared in regard to their flow and bioadhesive properties, in vitro drug release and antifungal/antibacterial activities. The viscosity of the formulations was found to be increased both with the increased concentration as well as with the increased molecular weight of chitosan whilst the drug release became slower. The antimicrobial activity was increased with the increased molecular weight of chitosan. The efficiency of Chx was significantly enhanced in presence of chitosan. Chitosans showed different antimicrobial activity depending on their properties, as well as the type of the strains tested.