This study was aimed at constructing a self-nanoemulsifying drug delivery system of buckwheat flavonoids and evaluating its antimicrobial activity. The construction of the nanoemulsion followed a pseudo-ternary phase diagram, and its particle properties (particle size, zeta potential, and surface morphology) and physicochemical parameters (turbidity, surface tension, pH value, conductivity, encapsulation efficiency, and stability) were evaluated. The antimicrobial potential of buckwheat flavonoids nanoemulsion was determined against Staphylococcus aureus, Escherichia coli, and Candida albicans and compared to the buckwheat flavonoids suspension. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) exhibited that the antimicrobial activity of the nanoemulsions and suspension increased while enhancing the drug concentration, and the antimicrobial activity of nanoemulsion was significantly higher than that of the suspension against those three bacteria. Agar disc diffusion test demonstrated that the inhibition zone diameter of the suspension was about 50% of the nanoemulsion against three bacteria. The time killing assay indicated that the IC50 of the nanoemulsion was significantly lower than that of the suspension. These results indicate that nanoemulsion is a promising drug delivery system, which can improve the antimicrobial activity of buckwheat flavonoids.