Topical drug applications to the external auditory canal (EAC) are one of the most important applications in Ear, Nose, and Throat (ENT) practice. In this study, we aimed to evaluate the histopathological, biochemical, and microbiological effects of oxygen-boric acid drops in the EAC. Eighteen albino Wistar rats were divided into three groups. The left ear was designated as the drop-treated ear, and the right ear was the control ear in each rat.  Group 1 rats were treated with Oxygen-boric acid drops, group 2 with ciprofloxacin drops, and group 3 with hydrogen peroxide drops for two weeks. For biochemical evaluation, the pH of the EAC was measured. Microbiological analysis was performed by culturing samples from both EACs.  Finally, both EACs underwent histopathological examination. Histopathologically, oxygen-boric acid ear drops had no adverse effect on the EAC mucosa. There was also no statistically significant difference amongst the groups in histopathological findings and bacterial growth.  While there was a statistically significant difference in pH was observed between the groups during the first week of treatment, no significant difference was found between the groups during the second week of treatment. Topical oxygen-boric acid, ciprofloxacin, and hydrogen peroxide can be used safely for EAC diseases due to their topical efficacy and fewer side effects. Topical drops should be chosen according to the disease, the patient's comorbidities, and the cost-effectiveness of ear drops.