The current study directly compares oleic acid’s and glycerol’s functionality as plasticizer and evaluates their compatibility and synergies with chitosan and/or Na-montmorillonite (NaMMT) in order to obtain films with antimicrobial and barrier properties and adequate performance for packaging applications. The effect of processing on the performance of the obtained films is also evaluated applying the solution casting and the heat-pressing methodologies. Overall it is shown that glycerol is more effective as plasticizer resulting in as high as 70% strain, compared to 26% strain obtained after 30 wt. % oleic acid’s addition. Furthermore, glycerol offers higher stability against water sorption with up to 15 times lower weight gain in films containing 30 wt. % glycerol. On the other hand oleic acid offers better barrier to water vapour transition with up to 3 times lower permeability rates. At the same time oleic acid addition improves the antimicrobial response of plain chitosan with up to 75% lower relative bacterial growth while glycerol’s addition does not lead to statistically significant changes. NaMMT contributes towards plasticization acting as plasticizer’s carrier diminishing the phase separation phenomena and leading into films with very broad Tg transitions at higher plasticizer contents (20 and 30 wt. %). Heat-pressing on the other hand offers great stability to water sorption with up to 40 times lower weight gain but inhibits the antimicrobial activity of the films which demonstrate measurable initial specific bacterial growth rate compared to almost 100% inhibition found in all “unpressed” films.