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This paper describes the preparation, characterization, and evaluation of honey/tripolyphosphate (TPP)/chitosan (HTCs) nanofibers loaded with capsaicin derived from the natural extract of hot pepper (<i>Capsicum annuum</i><i>L</i>.) and loaded with gold nanoparticles (AuNPs) as biocompatible antimicrobial nanofibrous wound bandages in topical skin treatments. The capsaicin and AuNPs were packed within HTCs in HTCs-capsaicin, HTCs-AuNP, and HTCs-AuNPs/capsaicin nanofibrous mats. In vitro antibacterial testing against <i>Pasteurella multocida, Klebsiella rhinoscleromatis,</i><i>Staphylococcus pyogenes,</i> and <i>Vibrio vulnificus</i> was conducted in comparison with difloxacin and chloramphenicol antibiotics. Cell viability and proliferation of the developed nanofibers were evaluated using an MTT assay. Finally, in vivo study of the wound-closure process was performed on New Zealand white rabbits. The results indicate that HTCs-capsaicin and HTCs-AuNPs are suitable in inhibiting bacterial growth compared with HTCs and HTCs-capsaicin/AuNP nanofibers and antibiotics (<i>P</i> < 0.01). The MTT assay demonstrates that the nanofibrous mats increased cell proliferation compared with the untreated control (<i>P</i> < 0.01). In vivo results show that the developed mats enhanced the wound-closure rate more effectively than the control samples. The novel nanofibrous wound dressings provide a relatively rapid and efficacious wound-healing ability, making the obtained nanofibers promising candidates for the development of improved bandage materials.