To determine the anti-inflammatory and antioxidant effects of quercetin (QCT) and/or resveratrol (RES) on human conjunctival (IOBA-NHC) and corneal (HCE) epithelial cell lines. IOBA-NHC and HCE cells were treated with QCT (0.5-25 μM), RES (0.5-50 μM) and a low-dose mixture of QCT (0.5 μM) and RES (5 μM) (QCT+RES) and stimulated with either TNF-α or ultraviolet (UV)-B radiation. Cytokine production (IL-6, IL-8, IP-10, and VEGF) was analyzed by an immune bead-based array, and intracellular reactive oxygen species (ROS) production was determined by a H2DCF-DA dye assay. Stimulation of IOBA-NHC and HCE cells with TNF-α induced an increase of IL-6, IL-8, and IP-10 secretion in both cell lines. Quercetin and RES decreased IL-6 and IP-10 secretion in a dose-dependent manner in both cell lines. Interleukin-8 secretion was also inhibited in a dose-dependent manner by QCT in HCE, but only at 20 and 25 μM QCT and 50 μM RES in IOBA-NHC and at 50 μM RES in HCE. QCT+RES decreased IL-6 and IL-8 secretion (P < 0.01 and P < 0.05, respectively) in IOBA-NHC cells. Ultraviolet-B induced a significant increase of ROS in both cell lines (P < 0.01 and P < 0.001 for IOBA-NHC and HCE cells, respectively), which was significantly decreased in a dose-dependent manner by QCT and RES in HCE cells. Reactive oxygen species production in IOBA-NHC cells was inhibited (P < 0.05) by 50 μM RES. Quercetin and RES have anti-inflammatory and antioxidant effects on IOBA-NHC and HCE cells. These in vitro data suggest that both polyphenols may have a therapeutic potential in the treatment of inflammatory ocular surface diseases.