This study was designed to formulate a polymeric mixed micelle (PMM) formulation to sustainably release fexofenadine (FEX) to treat allergic conjunctivitis effectively. A 3 factorial design was employed where the studied factors were PL90G amount (X) and Pluronic (F127 and P123) mixture ratio (X), and the dependent variables were entrapment efficacy (EE, Y, %), particle size (PS, Y, nm), zeta potential (ZP, Y, mV), and the percent of drug released after 6 h (Q6h, Y, %). The optimized formula was blended with a hydrogel base to develop an FEX-PMM hydrogel, where the safety and efficiency of this hydrogel were evaluated using in vivo studies. The EE% of FEX-PMM ranged from 62.15 ± 2.75 to 90.25 ± 1.48%, the PS from 291.35 ± 6.43 to 467.95 ± 3.60 nm, the ZP from -5.41 ± 0.12 to -9.23 ± 0.23 mV, and the Q6h from 50.27 ± 1.11 to 95.38 ± 0.92%. The Draize test results confirmed the safety of the FEX-PMM hydrogel. Furthermore, the FEX-PMM hydrogel showed rapid recovery in animals with induced allergic conjunctivitis compared to the free drug hydrogel. These results assure PMM's capability to deliver FEX to the conjunctival surface in a sustained pattern, consequently achieving better therapeutic outcomes.