Airborne particulate matter (PM₂.₅) contributes to oxidative damage of the ocular surface, particularly under dry eye-related hyperosmolar conditions. We evaluated the protective effects of a soluble extract derived from lyophilized human amniotic membrane patches (hAM-Te) in human corneal and conjunctival epithelial cells and THP-1 macrophages exposed to hyperosmolarity, industrial PM₂.₅, or both. Cell viability, migration, reactive oxygen species, nitrite production, total antioxidant capacity, and antioxidant enzyme activities were assessed. Combined hyperosmolarity and PM₂.₅ markedly impaired cell viability and migration while increasing oxidative and nitrosative stress. hAM-Te significantly improved cell viability and wound closure, reduced reactive oxygen species and nitrite levels, restored antioxidant capacity, and modulated endogenous antioxidant defenses. These findings demonstrate that hAM-Te attenuates redox imbalance and cellular injury induced by combined environmental and hyperosmolar stress, supporting its potential as a protective strategy against pollution-associated ocular surface damage.