Background and Objectives: More than a billion people worldwide suffer from chronic periodontitis. The primary etiological factor of periodontal diseases is dental plaque and the bacteria it contains, particularly Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans. Zinc, owing to its antibacterial properties, can be employed in periodontology. The objective of this review was to analyze scientific literature that examines the effects of zinc on periopathogens. Materials and methods: A systematic review protocol of scientific literature was designed following PRISMA recommendations. Data search was conducted in PubMed, Web of Science, and ScienceDirect databases. Full-text articles in English that examine the effects of zinc on periopathogens and were published between 2011 and 2021 were included. Results: Fifteen articles were included in the analysis based on inclusion criteria. ZnO exhibited antibacterial activity against P. gingivalis and P. intermedia (p < 0.001). The minimum inhibitory concentration against P. gingivalis was 10 μg/mL. ZnO demonstrated a significant antibacterial effect, as evidenced by inhibition zones of 15.10 mm for S. oralis, 13.36 mm for P. gingivalis, 12.98 mm for S. sanguis, and 14.01 mm for P. intermedia. Zn (II)-based polymers inhibited the ragA and ragB genes of P. gingivalis. Titanium dental implants coated with ZnO effectively disrupted the cell walls of P. gingivalis and A. actinomycetemcomitans. ZnO inhibited the growth of P. gingivalis within 2 h and the growth of F. nucleatum and P. intermedia within 3 h. ZnO exhibited nontoxic effects, and concentrations up to 0.8 mg/L increased cell survival rates by up to 90%. Conclusions: The analysis of the literature confirms the antibacterial action of zinc against periodontal pathogenic bacteria. At low concentrations, these substances do not exhibit cytotoxic effects on fibroblasts.