Objective To investigate the effects of curcumin on microRNA-125b (miR-125b) expression and cell damage in high glucose-induced human retinal pigment epithelial (RPE) cells. Methods ARPE-19 cells were cultured in vitro and divided into a control group, a high glucose group, a high glucose + curcumin group, a high glucose + miR-125b inhibitor group and a high glucose + inhibitor-negative control (NC) group. MTT assays were used to detect the activity of ARPE-19 cells. Annexin V-FITC/ PI double staining was used to detect apoptosis of ARPE-19 cells. A 2′ - 7′ dichlorofluorescin diacetate (DCFH-DA) probe loading method was used to detect the level of reactive oxygen species (ROS). An enzyme-linked immunosorbent assay (ELISA) was used to detect the level of superoxide dismutase (SOD) and RT-qPCR was used to detect the expression of miR-125b in cells. Results MTT assays showed that curcumin significantly improved the activity of ARPE-19 cells in a high glucose environment. Curcumin significantly reduced the rate of ARPE-19 cell apoptosis and ROS production in a high glucose environment, and increased the expression of SOD. RT-qPCR showed that curcumin significantly reduced the expression level of miR-125b. Conclusions Curcumin may reduce ROS production and increase SOD expression by down-regulating miR-125b expression. This would improve the antioxidant capacity of ARPE-19 cells and protect them from high glucose-induced cell damage.