Wound dressings are the primary barrier between the wound surface and the outer environment. Here we report the fabrication of cellulose acetate (CA)-Manuka honey (MH) composite nanofibrous mats as a biocompatible and antimicrobial wound dressing. CA mats with different quantities of MH were developed by electrospinning. The ATR-FTIR spectra confirm the inclusion of MH in the composite CA-MH nanofibrous mats. The fibers were continuous and bead-free with acceptable mechanical properties. The fiber diameter increased with an increase in MH content. Inclusion of MH in the electrospun composite CA-MH nanofibrous mats shows high efficacy to prevent bacterial growth on the wound surface. The MH loaded CA nanofiber mats showed good antioxidant abilities, while the ability to free radicalize the DPPH was dependent upon the factors of MH content in the fiber and the time of immersion in the DPPH solution. Besides, the nanofibrous mat's high porosity (85-90%) and WVTR values of 2600 to 1950 g/m2/day, suitable for wound breathability and the mats show high cytocompatibility to NIH 3T3 cell line in in vitro testing, proving to be effective for promoting wound healing.