Poly(l-lactide) (PLLA)/poly(d-lactide) (PDLA) stereocomplexes nanofiber mats with a range of PLLA:PDLA ratios were fabricated by electrospinning technique, using 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) as the solvent. Metronidazole (MNZ, 10% w/w) was incorporated into the nanofibers as the active compound for treatment of periodontal disease. The average diameter of electrospun nanofibers ranged from 177 to 824 nm. Differential scanning calorimetry and wide-angle x-ray diffraction confirmed stereocomplex formation in the PLLA:PDLA blends and successful incorporation of MNZ into the fibers. The fiber with the 50:50 PLLA:PDLA blend showed the highest stereocomplex formation, which decreased slightly with other blend ratios. The fiber tensile strength ranged from 3.9 to 12.9 MPa - it increased with higher stereocomplex formation. The entrapment efficiency of MNZ in the nanofiber mats was 82–99%. At least 30% of MNZ was released in the initial period followed by a sustained-release for up to 7 days. Nanofiber mats with greater stereocomplex formation exhibited higher initial burst and total release rate, and thus a greater antimicrobial activity. Most of the MNZ-loaded nanofiber mats demonstrated similar antimicrobial action against Porphyromonas gingivalis; there were comparable amounts of MNZ in the fibers. Moreover, the stereocomplex fibers showed slightly lower cytotoxicity than the fibers made from either of the single polymers. Therefore, the stereocomplex nanofiber mats were shown to be promising candidates for periodontal disease applications.