This study aims to investigate the effect of salidroside (SAL) on the proliferation, migration, and chemoresistance of ovarian cancer cells by regulating the forkhead box O3 (FOXO3)-forkhead box M1 (FOXM1) signaling axis. SKOV3 cells in logarithmic growth phase and cisplatin (DDP)-resistant ovarian cancer cell line SKOV3/DDP cells were selected. The SKOV3 cells were divided into the normal control group (cultured under normal conditions), the SAL low-dose, medium-dose and high-dose groups (intervened with 40, 80, and 160 μg/mL SAL respectively), the sh-FOXO3 group (transfected with the sh-FOXO3 plasmid), and the SAL + sh-FOXO3 group (treated with 160 μg/mL SAL after sh-FOXO3 transfection). The SKOV3/DDP cells were divided into the SKOV3/DDP group (without any treatment), the DDP group (0.3 μmol/L), the SAL+DDP group (treated with 0.3 μmol/L DDP and 160 μg/mL SAL in combination), and the SAL + DDP + sh-FOXO3 group (treated with 0.3 μmol/L DDP and 160 μg/mL SAL in combination and transfected with sh-FOXO3). CCK-8 assay and plate cloning assay were used to detect cell proliferation, and flow cytometry and Transwell assay were used to detect cell apoptosis and migration. The mRNA and protein expressions of FOXO3 and FOXM1 were determined by RT-qPCR and Western blot, respectively. The expression of FOXO3 and FOXM1 in the cancer tissues and adjacent tissues of ovarian cancer patients was determined by immunohistochemical method. The results showed that compared with the normal control group, the cell proliferation rate, number of migrated cells, number of colony formations, and FOXM1 protein expression in L-SAL group, M-SAL group and H-SAL group were decreased, while the apoptosis rate and FOXO3 protein expression were increased. Moreover, all these indicators showed a SAL concentration-dependent changes with the SAL concentration. In the sh-FOXO3 group, the cell proliferation rate, the number of migrating cells, the number of colony formation and the expression of FOXM1 protein in the sh-FOXO3 group were all increased, while the apoptosis rate and the expression of FOXO3 protein were both decreased (P < 0.05). Compared with the SAL high-dose group, the proliferation rate, number of migrated cells, number of colony formations, and the expression of FOXM1 protein in SKOV3 cells in the SAL + sh-FOXO3 group were all increased, while the apoptosis rate and FOXO3 protein expression were both decreased (P < 0.05). Compared with the SKOV3/DDP group and DDP group respectively, the proliferation rate of SKOV3 cells, scratch healing rate, colony formation number, and FOXM1 protein expression decreased in the SAL + DDP group, while the apoptosis rate and FOXO3 protein expression increased (P < 0.05); compared with the SAL + DDP group, the apoptosis rate and FOXO3 protein expression of SAL + DDP + sh-FOXO3 group were decreased, while the remaining indicators mentioned above all increased (P < 0.05). The positive expression rate of FOXO3 in ovarian cancer tissues (81.25%) was higher than that in adjacent tissues (25.00%), while the positive expression rate of FOXM1 in cancer tissues (14.58%) was lower than that in adjacent tissues (77.08%) (P < 0.05). In summary, SAL can inhibit the proliferation, migration, and chemosensitivity of ovarian cancer cells, and enhance the chemoresistance of ovarian cancer cells to DDP by activating the FOXO3-FOXM1 signaling pathway.