Antibiotics are used for postsurgical wound healing purposes but unfortunately, resistance against them demands some alternatives for quick recovery. Sepsis of wounds is a challenge for medical as well as veterinary professionals. Nanoparticles have significant advantages in wound treatment and drug resistance reversal. This study was conducted to appreciate emerging alternates of antibiotics like zinc oxide nanoparticles and plant extracts in topical application. Zinc oxide is considered a good wound healer and its nanoparticles are easy to access. So, the efficacies of zinc oxide nanoparticles and sweet flag plant extract ointments were tested to compare modern and traditional therapeutics as sweet flag is considered a pure medicinal plant. Rabbits were selected for this study due to the healing properties of their skin. Wounds were inflicted on the thoracolumbar region and treated for 29 days post-surgically daily with normal saline and the ointment of zinc oxide nanoparticles and sweet flag extract ointment, prepared in a hydrophilic solvent. Wound shrinkage was observed daily and histopathological analysis was made and results were compared. Zinc oxide nanoparticles ointment showed the most satisfactory results for every parameter included in the study. No side effects of its topical application were observed. Healing was normal without any complications. The preparations of zinc oxide nanoparticles may help in the era of antibiotic resistance as topical drugs in the future.