Granulosa cells (GCs) control follicular development and are important for female reproduction. Resveratrol (Res) was considered as an antioxidant and Sirt1 inducer. Hydrogen peroxide (H2O2) is the classical reagent to study oxidative stress. The study was conducted to investigate the role of Res against H2O2 in human luteinised granulosa cells (LGCs). The LGCs in the H2O2 group were treated with 100μmol/L H2O2 for 24h. The LGCs in the Res group were treated with 50μmol/L Res for 2h, followed by H2O2. The LGCs in the Sirt1 blockage group were treated with 2.5μmol/L EX527+50μmol/L Res for 2h, followed by H2O2. Results showed that Res significantly increased LGCs viability in H2O2-induced LGCs. The apoptotic rate and ROS in the H2O2 group was higher and the antioxidant enzyme activity was lower compared with other groups. Following the Res, the apoptotic rate and ROS level were reduced and the antioxidant enzyme activity were increased. In the Res blockage group, no significant alterations in the cell apoptosis, ROS and antioxidant enzyme activity were observed compared with the H2O2 group. The Res group had a Caspase-3 downregulation and Sirt1 upregulation compared with the other groups. In conclusion, Res had a protective effect against the H2O2-induced LGCs, and the mechanism may be associated with Sirt1.