Background: Having an adverse impact on systemic health, periodontitis is an inflammatory disease which is characterized by the loss of integrity in tooth-supporting tissues. Middle-aged human (MAH) have been reported to have a higher incidence of periodontitis and a greater extent of bone loss. Although the similar dental anatomy and physiology as humans, whether middle-aged monkey (MAM) has the same disease phenotype as MAH is unclear. Furthermore, literature comparing the periodontal status between MAH and MAM is limited. Methods: Therefore, four female middle-aged Macaca fascicularis and five middle-aged woman were used to evaluate the periodontal status before evaluating possible mechanism that may explain the difference between these two primates. CBCT examination and histological analysis were performed to characterize the periodontal condition, while 16s rRNA sequencing was done to explore the oral microbial profiles of two groups. Results: The present study revealed a more severe disease phenotype in MAH than in MAM, along with significantly higher levels of alveolar bone loss and increased blood vessels and inflammatory cells infiltration. High-throughput gene sequencing demonstrated that the diversity of salivary microorganisms in MAH was lower than that of MAM. In addition, at the phylum level, the relative abundance of Proteobacteria in the MAH was higher than MAM, while Bacteroidetes showed a totally opposite trend. At the genus level, the relative abundances of Alloprevotell, Aggregatibacter, Haemophilus, Gemella and Porphyromonas in the MAH group were significantly less than that of the MAM group. Conclusions: Altogether, these results demonstrated a potential link that may explain for the difference in inflammatory status in the oral cavity of MAH and MAM – the oral microbiota, prompting further investigation to explore specific roles of these bacterial population in the maintenance of oral health.