(1) Background: The amino acid arginine is now receiving great attention due to its potential anti-caries benefits. The purpose of this in vitro study was to evaluate the shear bond strength (SBS), ultimate tensile strength (UTS), and antimicrobial potential (CFU) of two arginine-containing orthodontic resin cements. (2) Methods: Forty bovine incisors were separated into four groups (n = 10): Orthocem, Orthocem + arginine (2.5 wt%), Transbond XT, and Transbond XT + arginine (2.5 wt%). The brackets were fixed to the flat surface of the enamel, and after 24 h the SBS was evaluated using the universal testing machine (Instron). For the UTS test, hourglass samples (n = 10) were made and tested in a mini-testing machine (OM-100, Odeme). For the antibacterial test (colony forming unit-CFU), six cement discs from each group were made and exposed to Streptococcus mutans UA159 biofilm for 7 days. The microbiological experiment was performed by serial and triplicate dilutions. The data from each test were statistically analyzed using a two-way ANOVA, followed by Tukey’s test (α = 0.05). (3) Results: The enamel SBS mean values of Transbond XT were statistically higher than those of Orthocem, both with and without arginine (p = 0.02033). There was no significant difference in the SBS mean values between the orthodontic resin cements, either with or without arginine (p = 0.29869). The UTS of the Transbond XT was statistically higher than the Orthocem, but the addition of arginine at 2.5 wt% did not influence the UTS for either resin cement. The Orthocem + arginine orthodontic resin cement was able to significantly reduce S. mutans growth, but no difference was observed for the Transbond XT (p = 0.03439). (4) Conclusion: The incorporation of arginine to commercial orthodontic resin cements may be an efficient preventive strategy to reduce bacterial growth without compromising their adhesive and mechanical properties.

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