D-amino acid-based surfactants (D-AASs) were synthesized and their antimicrobial activity was evaluated. N-α-lauroyl-D-arginine ethyl ester hydrochloride (D-LAE), D-proline dodecyl ester (D-PD), and D-alanine dodecyl ester (D-AD) were found to have antibacterial activity against both Gram-positive and -negative bacteria, but less efficacy against Gram-negative bacteria. For these reasons, combining antimicrobial agents with nanoparticles is a promising technique for improving their antibacterial properties to eliminate drug-resistant pathogens. D-LAE coated on gold (AuNP) and silica (SiNP) nanoparticles has more efficient antibacterial activity than that of D-LAE alone. However, unlike D-LAE, D-PD has enhanced antibacterial activity upon being coated on AuNP. The antibacterial D-AASs and their nanocomposites with nanoparticles were synthesized in an environmentally friendly manner and are expected to be valuable new antimicrobial agents against multidrug-resistant (MDR) pathogens.