Purpose: To investigate viscosity and wettability of hyaluronic acid (HA) solutions according to supplementation of lysozyme and/or peroxidase, and different ionic strength and pH conditions. Methods: Solutions containing HA were prepared using distilled deionized water (DDW) and simulated salivary buffer (SSB) in different conditions. Different concentrations of hen egg-white lysozyme and bovine lactoperoxidase was added into HA solutions. HA solutions with antimicrobials in different ionic strength and pH conditions were prepared. Viscosity was measured using cone-and-plate digital viscometer at six different shear rates and wettability on acrylic resin and Co-Cr alloy was determined by contact angle. Results: The viscosity values of HA dissolved in DDW were decreased in order of HA, HA containing lysozyme, HA containing peroxidase, and HA containing lysozyme and peroxidase. The viscosity values for HA in DDW were decreased as the concentration of lysozyme and/or peroxidase increased. However, the viscosity values for HA in SSB showed no significant changes according to the concentration of lysozyme and/or peroxidase. The viscosity values of HA solutions were inversely proportional to ionic strength and pH. The contact angle of HA solutions showed no significant differences according to tested surface materials, addition of lysozyme and/or peroxidase, and different ionic strength and pH conditions. Contact angles on acrylic resin by HA solutions in all tested conditions were much higher than those by human saliva. Conclusions: The rheological properties of HA supplemented with lysozyme and/or peroxidase in different ionic strength and pH conditions were objectively confirmed, indicating the possibility of HA with lysozyme and/or peroxidase as main components in the development of effective saliva substitutes.