Purpose <p>This study aimed to evaluate a novel microemulsion ion-activated gel system for the ophthalmic delivery of coenzyme Q10 (CoQ10).</p> Methods <p>Various CoQ10 microemulsion ion-activated formulations were prepared and fully assessed for physical and chemical parameters, assay and related substances, in vitro release, rheological properties, in vitro cytotoxicity and ophthalmic retention. A preliminary pharmacokinetic study was also performed in rabbits.</p> Results <p>The formulations met the specified criteria, showing a droplet size of 24.5 ± 2.0&#xa0;nm for microemulsions, increasing slightly to 39.6 ± 3.5&#xa0;nm for the microemulsion gels. They exhibited a 24-hour sustained in vitro release (80.0% ± 3.2%) and increased viscosity upon contact with artificial tears containing Ca²⁺ and K⁺ ions. The no-film dissolution method and in vitro models indicated first-order release kinetics (<i>r</i> = 0.987). The preparations demonstrated good tolerance and non-irritating properties, with a Draize score of 0–0.55 in rabbits, and provided a 2-hour extension in drug retention on the ocular surface compared with microemulsions alone. In ultraviolet B (UVB)-exposed rats, corneal epithelial damage was reduced and antioxidant marker levels (superoxide dismutase, malondialdehyde) were significantly improved.</p> Conclusion <p>This novel system is a promising preparation for ophthalmic CoQ10 delivery, offering sustained release and protection against UVB-induced corneal damage.</p>