<p>The present research is focussed on formulation and optimization of clove oil-based otic nanoemulsion for the effective delivery of ofloxacin to improve therapeutic efficacy and evade limitations of traditional ear drops. The screening of solubility showed that the clove oil, Tween 20, and propylene glycol were selected as appropriate excipients, and pseudo-ternary diagrams demonstrated 3:1 and 2:1 S_mix ratios generated wide nanoemulsion regions. The formulations were developed by high-pressure homogenization and characterized for pH, viscosity, and drug content, transmittance, dispersibility, particle size, polydispersity index, zeta potential, and stability. The selected formulations NE4 and NE8 showed nanometer sized droplets, and greater negative zeta potential, suggesting exceptional stability. The formulation demonstrated high drug content (&gt; 95%), suitable pH and optical clarity confirming compatibility with otic tissues. The in vitro release studies exhibited considerably higher and sustained release of ofloxaxin in comparison with pure drug suspension, owing to the increased surface area and improved solubilization in the nanoemulsion system. The stability testing for 30 days ensured the robustness with no significant changes in the physicochemical properties. The outcomes indicates that the clove oil-based otic nanoemulsion is potential delivery system for ofloxacin, with possible capability of enhancing bioavailability, and reduced dosing frequency.</p>