Aggregatibacter actinomycetemcomitans(A.a) is an oral pathogen, whose virulence relies on Cdt toxins, a Tad/Flp adherent and LPS. This study evaluated a comprehensive effect of methanol extract of Saliva miltiorrhiza(MESM) against A.a. Antibacterial activity, attachment and antioxidant assay were investigated. Inhibition of expression of virulence, inflammatory/osteoclastogenic genes and IL-1β production using ELISA were performed. The MIC of MSEM was 250 μg/mL and aggregation decreased by 21.20 ± 3.69% at 62.5 μg/mL of MSEM. At 1 mg/mL of MESM, ABTS, DPPH and superoxide radical scavenging activities were 84.01 ± 0.74%, 74.71 ± 2.14% and 50.97 ± 1.12% respectively. At 125 μg/mL of MSEM, expression of qseC and cdtA were decreased by 66.1% and 60.1%, respectively. In case of 100 MOI of A.a infected YD-38 cells, RQ value of RANKL and IL‑8 were decreased from 3.40 ± 0.20 to 0.704 ± 0.018 and from 17.32 ± 1.74 to 5.50 ± 0.50 at 50 μg/mL of MESM. In case of 100 MOI of A.a infected THP-1 cells, RQ value of IL-1β was decreased from 6,440 ± 185 to 3,366 ± 83 at 125 μg/mL of MESM. IL‑1β production was reduced from 18.62 ± 1.30 to 10.20 ± 1.02 pg/mL in THP-1. Collectively, MESM showed antimicrobial activity, antioxidant capacity, suppression of virulence genes and host inflammatory gene expression, supporting MESM as a candidate for prevention or treatment of oral microbial diseases.