Objective To explore the correlation between the levels of serum miR-485 and miR-205-5p and the efficacy of chemotherapy in patients with ovarian cancer (OC). Methods A retrospective study was conducted on 114 patients with OC admitted to Nanyang Central Hospital from December 2020 to December 2023. These patients were divided into three groups based on the effect of chemotherapy after four cycles: remission group (59 cases), stable group (31 cases), and deterioration group (24 cases). The serum levels of miR-485 and miR-205-5p before chemotherapy, after two cycles of chemotherapy and after four cycles of chemotherapy were compared among the three groups, and the correlation was analyzed. The predictive value of combined detection of serum levels of miR-485 and miR-205-5p for chemotherapy effect in patients with OC was analyzed. Results The serum miR-485 level in the deterioration group was lower than that in the stable group and the remission group, and the stable group was lower than that in the remission group (P<0.05), the serum miR-205-5p level in the deterioration group was higher than that in the stable group and the remission group, and the stable group was higher than that in the remission group, the differences were statistically significant (P<0.05); serum miR-485 level before chemotherapy<after 2 cycles of chemotherapy<after 4 cycles of chemotherapy, serum miR-205-5p level before chemotherapy>after 2 cycles of chemotherapy>after 4 cycles of chemotherapy, the differences were statistically significant (P<0.05); Serum miR-485 level was negatively correlated with the effect of chemotherapy, and serum miR-205-5p level was positively correlated with the effect of chemotherapy, the differences were statistically significant (P<0.05); the area under the ROC curve (AUC) of serum levels of miR-485 and miR-205-5p combined to predict the deterioration of chemotherapy results in patients with OC after two cycles of chemotherapy was 0.846, and the best diagnostic sensitivity was 87.50%, specificity was 84.44%, the differences were statistically significant P<0.05). Conclusion The serum levels of miR-485 and miR-205-5p are closely related to the effect of chemotherapy in patients with OC, which can provide an effective reference for clinical prediction of chemotherapy effect.