This study aims to describe the oral microbiome diversity and prevalence of ARGs in periodontal health and disease. Background The human oral cavity harbors a complex microbial community known as the oral microbiome. These organisms are regularly exposed to selective pressures, such as the usage of antibiotics, which drive evolution and acquisition of antibiotic resistance genes (ARGs). Resistance among oral bacteria jeopardizes not only antibiotic therapy for oral infections, but also extra-oral infections caused by bacterial translocation. Methods We carried out a cross-sectional investigation. Saliva and subgingival plaque samples were collected during a clinical exam. 16S rRNA gene sequencing was performed to assess microbial diversity. Resistance genes were identified through PCR assays. Results Of the 110 participants, only 22.7% had healthy periodontium, while the majority was diagnosed with gingivitis (55.4%) and chronic periodontitis (21.8%). The composition of the oral microbiota differed from healthy and diseased samples, being Streptococcus spp. and Rothia spp. predominant in periodontal disease. Regarding ARGs, 80 (72.7%) samples were positive for at least one of genes screened, erm being the most frequent variant (58.2%), followed by bla TEM (16.4%), mecA (2.7%), pbp2b and aac(6 ') (1.8%). Neither genes coding resistance to carbapenems nor metronidazole were detected. Conclusions Our findings indicate that there are no significant differences in terms of taxonomic enrichment between healthy and diseased oral microbiomes. However, samples retrieved from healthy patients had a more diverse microbial community, whereas diseased samples have