The aim of this study was to develop optimal formulation of chitosan-based gel suitable for incorporation of liposomes with hydrophilic and lipophilic active ingredients (diltiazem chloride and azithromycin dihydrate), and to perform physical characterization of the optimized hydrogels. Hydrogels containing different types and weight ratio of chitosan and lactic acid were prepared, and the preparation method was optimized. Liposomes with diltiazem chloride and azithromycin dihydrate composed of the different (phospho)lipid components were prepared by film method, proliposome and polyol dilution method, respectively. Homogenization of liposome dispersions was performed by extrusion through polycarbonate membranes. All the liposomes were physically characterized by determining mean diameters, polydispersity indexes and zeta potentials. Different types of the liposomes were incorporated into 2,5% chitosan gel (optimal gel formulation) and the mechanical properties of the hydrogels were evaluated by determining the textural characteristics of the gels: hardness, cohesiveness and adhesiveness. It was shown that the (phospho)lipid composition, presence of surfactant and cosolvent as well as lipophilicity of the incorporated drug contribute to the mehanical properties of the liposomal hydrogels. These properties influence: application of the formulation to the skin or mucosa (hardness), removal of the formulation from container/tube (cohesiveness) as well as the retention of the formulation at the site of administration (adhesiveness).