Epithelial Ovarian Cancer (EOC) is the 8th most common cause of death from cancer in women worldwide. The disease is characterized by advanced presentation, multiple relapses, resistance to treatment, and ultimately poor prognosis. Thus, there is an urgent need to support research to identify effective drugs that may have cytotoxic properties and may help overcome the resistance to frontline chemotherapy. Such compounds may be obtained from natural resources. Oman's extensive coastline may contain marine species from which bioactive natural chemicals can be harvested. In a previous study, 40 Omani marine compounds were screened for the anti-cancer activity using the MCF-7 breast cancer cell line. Five compounds, including MalforminA1 (MA1), Hymenialdisine, and Sarcophyton sp. extracts, were found to have significant anti-cancer activity. Objective: The present study aimed to test these compounds' anti-cancer activity and potential on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines. In addition to choose one compound with maximum activity and study whether this compound will help overcome resistance to cisplatin. In addition, we sought to study this compound's putative mechanism of cytoxicity. Results: Using AlamarBlue and Cell Counting Kit (CCK8) assay, our results revealed that MalforminA1 exhibited the highest cytotoxicity on A2780S and A2780CP cell lines with IC50 values of 0.23µM and 0.34µM respectively, whereas 10Z-hymenialdisine exhibited a very low cytotoxic effect. Both the DNA fragmentation test and Flow cytometry analysis confirmed the cytotoxic effect of MA1 and the synergism of MA1 and cisplatin. Several key genes and proteins were examined using RT-qPCR, western blot, and immunofluorescence techniques to investigate the mechanisms of cell death induced by MA1 in ovarian cancer cells. The results suggest that in addition to apoptosis, there are other pathways that MA1 follows to kill ovarian cancer cells. A significant reduction in the pro-apoptotic genes BAD, BAX, FADD, TRADD, and RIP1, and a significant increase in the expression of γ-H2AX and caspase1, activation of NF-Kβ following the treatment indicates that MA1 causes DNA damage in inflammatory-related programmed cellular death. Moreover, the data suggest the involvement of the autophagy cellular death pathway as seen by the conversion of LC3B-I protein to the lipidated protein LC3B-II after MA1 treatment. Furthermore, MA1 was found to suppress several vital biological process-related genes like Yap/Taz, Stat3, and Akt, as well as to affect the cell dynamics by suppressing cellular cytoskeleton-related genes such as α-Tubulin, β-Tubulin, Vimentin, β-actin, GAPDH, Beta-catenin. Conclusion: MA1 induces significant cytotoxicity at very low concentrations and overcomes resistance to cisplatin in cisplatin-resistant cell lines. Further investigations are required to fully elucidate the mechanism of action of cytotoxicity.