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Background: Motor and intellectual disabilities (MIDs) represent a great challenge for maintaining general health due to physical and cognitive limitations, particularly in the maintenance and preservation of oral health. Silver nanoparticles (AgNPs) have emerged as a promising therapeutic tool for bacterial control, including oral biofilms; however, knowledge of the bactericidal effectiveness of oral biofilms from patients with MIDs is insufficient. This study aims to determine the antimicrobial effect of AgNPs on different oral biofilms taken from patients with and without MIDs. Methods: Two sizes of AgNPs were prepared and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Through consecutive sampling, biofilm samples were collected from 17 subjects with MIDs and 20 subjects without disorders. The antimicrobial effect was determined by obtaining the minimum inhibitory concentration (MIC) of AgNPs, and the identification and distribution of oral bacterial species were determined by polymerase chain reaction (PCR). Finally, correlations between sociodemographic characteristics and the antimicrobial levels of AgNPs were also explored. The values of the MIC results were analyzed with IBM-SPSS software (version25) using non-parametric tests for independent groups and correlations, with statistical significance being considered as p < 0.05. Results: Both sizes of AgNPs exhibited tight particle size distributions (smaller: 10.2 ± 0.7 nm; larger: 29.3 ± 2.3 nm) with zeta potential values (−35.0 ± 3.3 and −52.6 ± 8.5 mV, respectively) confirming the stability that resulted in little to no agglomeration of nanoparticles. Although both sizes of AgNPs had good antimicrobial activity in all oral biofilms, the smallest particles had the best antimicrobial effects on the oral biofilm samples from patients with and without MIDs, even better than chlorhexidine (CHX) (p < 0.05). Likewise, the patients with disabilities showed higher levels of antimicrobial sensitivity to AgNPs compared with CHX (p < 0.05). Although the microorganisms included in the biofilms of females had a statistically higher growth level, the AgNP antimicrobial effect was statistically similar in both genders (p > 0.05). The most frequent bacteria for all oral biofilms were S. mutans (100%), P. intermedia (91.6%), T. forsythia (75.0%), T. denticola (75.0%), P. gingivalis (66.6%), F. nucleatum (66.6%), S. sobrinus (50.0%), and A. actinomycetemcomitans (8.3%). Conclusions: AgNPs exhibited considerable antimicrobial potential to be used as a complementary and alternative tool in maintaining and preserving oral health in patients with MIDs.