Purpose <p>In this randomized clinical trial, we examined the incorporation of nanogold particles into polymethyl methacrylate denture bases and compared these modified bases with conventional ones in mandibular implant-retained overdentures, focusing on microbiological growth and adhesion characteristics.</p> Methods <p>In this study, twenty-two male patients who were completely edentulous participated in a rehabilitation program involving mandibular overdentures retained by two dental implants placed in the canine area. The subjects were categorized into two equal groups, each comprising eleven patients. Group I received mandibular overdentures fabricated from conventional acrylic denture bases, whereas Group II received mandibular overdentures with bases that had undergone nanogold treatment. Microbial growth and colonization were evaluated around the implant’s necks and the fitting surface of each patient’s mandibular dentures. Three types of bacteria were studied: Candida albicans, Escherichia coli, and Streptococcus mutans. The mean difference in the counts of bacteria before the denture was inserted and after two, four, and six months has been calculated and analyzed statistically.</p> Results <p>Regarding colony count (log 10 CFUs/mmL), there was a significant difference between the research groups. Group II had significantly lower values measured at 2, 4, and 6 months for Candida albicans, Escherichia coli, and Streptococcus mutans, respectively, than group I.</p> Conclusion <p>The addition of gold nanoparticles to PMMA denture bases was of greater benefit in inhibiting microbial growth than conventional acrylic resin bases.</p>