Colonization of auto-polymerized acrylic resin by pathogenic Candida albicans is a common problem for denture users. In this study, zinc-modified phosphate-based glass was introduced into an auto-polymerized acrylic resin at concentrations of 3, 5, and 7 wt.%. The mechanical or physical properties (flexural strength, elastic modulus, microhardness, and contact angle), surface morphology of the resultant materials, and the antimicrobial effect on C. albicans were investigated. There were no statistical differences in the mechanical properties between the control and the zinc-modified phosphate-based glass samples (p > 0.05); however, the number of C. albicans colony-forming units was significantly lower in the control group (p < 0.05). Scanning electron microscopy revealed that C. albicans tended not to adhere to the zinc-modified-phosphate-based glass samples. Thus, the zinc-modified materials retained the advantageous mechanical properties of unaltered acrylic resins, while simultaneously exhibiting a strong antimicrobial effect in vitro.