Products have been developed to provide palliation for persons with dry mouth. In addition to mouth-wetting agents, some products incorporate antimicrobial constituents with the goal of improving oral microbial defenses. The aim of this in vitro study was to investigate the potential antimicrobial and antifungal effects of two commercially available saliva substitutes on Streptococcus mutans, Lactobacillus acidophilus, and Candida albicans by using the agar-well diffusion method. Antimicrobial activity as measured by the size of the inhibition zone growth for S. mutans and L. acidophilus was observed only with Biotene Dry Mouth Oral Rinse® and BioXtra® gel. The zone of inhibition of Biotene Dry Mouth Oral Rinse was larger than that of BioXtra gel (p= 0.00, p < 0.01). No anticandidal effect was seen with any of the test products. The pH of the preparations, the variations between the amount of active ingredients within the products, and the potential antimicrobial effects of inactive ingredients should be investigated to determine the factors that impacted microbial inhibition.