Ovarian cancer has gradually become one of the commonest gynecological tumor in the world. Although various therapies have been developed by researchers, the chemoresistance of ovarian cancer is still a huge challenge. MircroRNAs (miRNAs) have been widely studied due to their anti-oncogenic functions. MiR-378a-3p has been reported to sensitize breast cancer cells to chemotherapy. Here, we hypothesized that miR-378a-3p is a potential chemosensitizer in ovarian cancer. Firstly, miR-378a-3p was uncovered to down-regulated in ovarian cancer tissues and cell lines through using qRT-PCR analysis and northern blot analysis. According to the result of Kaplan Meier analysis, low expression of miR-378a-3p is closely associated with unfavorable prognosis of ovarian cancer patients. Subsequently, gain-of function assays indicated that miR-378a-3p suppressed cell proliferation and promoted cell apoptosis. Moreover, miR-378a-3p was found to enhance cisplatin sensitivity of ovarian cancer cells. Mechanism investigations suggested that MAPK1 and GRB2 are two targets of miR-378a-3p. Finally, rescue assays revealed that MAPK1 and GRB2 can reverse the effects of miR-378a-3p on chemosensitivity of ovarian cancer cells. In conclusion, miR-378a-3p enhanced the sensitivity of ovarian cancer cells to cisplatin through targeting MAPK1 and GRB2.