Purpose: To evaluate the antimicrobial activity of effervescent tablets on the surfaces of cobalt-chromium (Co-Cr) and heat-polymerized resin. Materials and Methods: From a metal matrix, 55 circular wax patterns (Ø 12 × 3 mm) were obtained and cast in Co-Cr alloy. Muffles for acrylic resin were prepared from circular wax patterns (Ø 20 × 5 mm). The metal specimens were positioned in the muffle, and the resin was pressed into its surroundings to simulate the composition of a removable partial denture (RPD). The mixed specimens were sterilized and contaminated with Streptococcus mutans, Staphylococcus aureus, Candida albicans, and Candida glabrata, composing a multispecies biofilm, and subsequently immersed according to the manufacturer's instructions in four cleansing solutions: Polident 3 Minute denture cleanser (P3M), Polident for Partials (PP), Corega Tabs (CT), and NitrAdine (Ni); as well as distilled water (positive control) and no contamination (negative control). After cleansing, viable microorganisms were quantified by counting the number of colony-forming units (CFU/mL). From the CFU values, log10^{(CFU + 1)} values were calculated for statistical analysis. Kruskal-Wallis test with Dunn post hoc test were performed (α = .05). Results: There was a significant reduction (P = .001) of S mutans after immersion in Ni (median [95% CI] 3.27 [2.92; 3.45]) compared to the CT (3.86 [3.75; 4.01]) and control (4.08 (3.73; 4.22]) groups, while the PP (3.63 [3.28; 4.11]) and P3M (3.83 [3.61; 4.04]) groups presented an intermediate action. The effervescent tablets did not present antimicrobial action against S aureus (P = .537), C albicans (P = .795), or C glabrata (P = .519). Conclusion: Ni exhibited moderate antimicrobial action. The effervescent tablets did not promote reduction of multispecies biofilm, and their daily use should be carefully considered.