ObjectiveTo develop more efficient approaches for inhibiting the growth of Fusobacterium nucleatum (F. nucleatum).MethodsThe effects of inhibiting Fusobacterium nucleatum of D-phenyllactic acid (D-PLA) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were explored by the concentration gradient method, the effect of D-PLA combined with HP-β-CD on inhibiting the growth of Fusobacterium nucleatum was explored by the checkerboard method, and the molecular structure mechanism underlying drug combination effects was analyzed. During the experimental process, the spectrophotometry was used to test the growth of F. nucleatum within 48 hours, and then the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by integrating the growth curve and the plate inoculation results to evaluate the antibacterial effect. The conjugation molecular structure model was constructed by the quantum chemical QM calculations combined with energy data.ResultsD-PLA had inhibitory effect on the growth of F. nucleatum, the MIC was 0.6 mg/mL while MBC was 4.5 mg/mL. The MIC of HP-β-CD was 1.0 mg/mL against Fusobacterium nucleatum.ConclusionThe combination of D-PLA and HP-β-CD shows a fractional inhibitory concentration (FIC) index of 0.25 (<0.5), forms an envelope structure at the molecular level, and exhibits synergistic antibacterial effects against Fusobacterium nucleatum.