During the last two decades, new drug delivery strategies have been invented that have been able to solve microbial resistance against antibiotics. The goal of the current report was to assess the antimicrobial effects of nano-catechin gels against clinically isolated Porphyromonas gingivalis, one of the main causes of periodontal disease. Catechin-loaded chitosan nanoparticles were prepared by adding a catechin solution to a chitosan solution. Then, the mean particle size and the mean surface charge (zeta potential) of the nanoparticles were detected through photon correlation spectroscopy and zeta sizer, respectively. Nano-catechin gels (1000, 500, 250, 125, 62.5, and 31.2 µg/mL) were prepared, and the antimicrobial assay was performed against clinically isolated Porphyromonas gingivalis (P. gingivalis). The clinically obtained P. gingivalis isolates were obtained from periodontitis patients (N = 15). The consequences are specified as descriptive indices. The normality of data was detected by the Shapiro–Wilk test. Then, to compare the data between groups (with a p value < 0.05 as the significance level), SPSS software (version 22) was used via a Mann–Whitney U test. The results showed a nanometer particle size range and a positive zeta potential for the prepared nanoparticles. All the concentrations (1000, 500, 250, 125, 62.5, and 31.2 µg/mL) of nano-catechin gels showed sustained release patterns and were non-toxic against dental pulp stem cells as well. There were no significant differences between the minimal inhibitory concentrations (MICs) for nano-catechin gel (test group) and Chlorhexidine (control group) against 15 isolates (p > 0.05). Then, two groups showed similar antimicrobial effects. The similar antimicrobial activity of catechin nanoparticles and Chlorhexidine, as a potent antimicrobial agents, against clinically isolated P. gingivalis showed that catechin nanoparticles can be used as a potent antimicrobial material for the treatment of periodontal diseases in the near future.