Dental caries is an infectious oral disease caused by the presence of different bacteria in biofilms. Multidrug resistance (MDR) is a major challenge of dental caries treatment. Swabs were taken from 65 patients with dental caries in Makkah, Saudi Arabia. Swabs were cultivated on mitis salivarius agar and de Man, Rogosa, and Sharpe (MRS) agar. VITEK 2 was used for the identification of isolated bacteria. Antibiotic susceptibility testing of the isolated bacteria was performed using commercial antibiotic disks. Ulva lactuca was used as a reducing agent and cellulose source to create nanocellulose and Ag/cellulose nanocomposites. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction spectroscopy (XRD) were used to characterize nanocellulose and Ag/cellulose nanocomposites. The results showed that most bacterial isolates were spp., followed by spp. on mitis salivarius media. spp. and group f-1 were the bacterial isolates on de Man, Rogosa, and Sharpe (MRS) media. The antibiotic susceptibility test revealed resistance rates of 77%, 93%, 0, 83%, 79%, and 79% against penicillin G, Augmentin, metronidazole, ampicillin, ciprofloxacin, and cotrimoxazole, respectively. Ag/cellulose nanocomposites and Ag/cellulose nanocomposites with fluoride were the most effective antibacterial agents. The aim of this work was to assess the antibacterial activity of Ag/cellulose nanocomposites with and without fluoride against bacteria isolated from the oral cavities of patients with dental caries. This study demonstrated that Ag/cellulose nanocomposites have antibacterial properties against multidrug-resistant bacteria that cause dental caries.