The aim of this work was to formulate and evaluate nalidixic acid for the first time in different topical ointment bases. Among different ointment formulations, hydrocarbon base achieved the lowest release, while water-soluble base achieved the highest release. The presence of both isopropanol as cosolvent and nalidixic acid-sodium benzoate solid dispersion in formula (W8) enhanced both the release and the antibacterial activity of nalidixic acid compared to ointment formula (W5) containing neither of them. A stability study was also performed where no significant change in pH or drug content was observed in all stored formulations (W5 and W8). Stability was further checked by thin-layer chromatography (TLC). After clinical application in impetigo, it was found that the presence of isopropanol and nalidixic acid-sodium benzoate solid dispersion in ointment formulation (W8) caused a significant reduction in the mean time of healing (only four days) in impetigo patients.