Oxidative stress has been recognized as an important mediator in the pathogenesis of age-related cataracts; using antioxidant supplements is one plausible strategy to protect the antioxidative defense system against oxidative stress. Ghrelin administration is expected to reduce ROS, preventing the onset of different diseases. The role of ghrelin, if any, in protecting against oxidative stress in HLECs has never been examined. In the present study, we investigated the effects of ghrelin against H2O2-induced oxidative stress and the associated molecular mechanisms in HLECs and rat lenses. The results showed that pretreatment with ghrelin reduced H2O2-induced cellular apoptosis and ROS accumulation, increased the expression levels of SOD and CAT, and decreased the expression level of MDA. The morphological examination showed that the ghrelin-treated lens organ culture maintained transparency. This is the first report to show that ghrelin can protect HLECs from H2O2-induced oxidative stress. Our findings suggest that ghrelin may prevent the progression of cataracts, which has treatment value for ophthalmologists.