Background: Ovarian cancer (OvCa) malignancy is a widespread type of cancer with a poor prognosis contributed by resistance developed against platinum-based drugs. The use of phytochemicals has been an innovative key for the treatment of OvCa. The antiproliferative properties of Thymoquinone (TQ) have indicated remarkable effects on targeting multiple pathways potentially leading to apoptosis. The aim of the study augmenting the effects of TQ in overcoming cisplatin (CDDP) induced drug resistance in SKOV-3 cells. Methods: The cells were treated with increasing doses of TQ in a time-dependent manner. The apoptotic bodies were analyzed by DAPI while the mitochondrial membrane potential was analyzed by Rh-123. The clonogenic assay was carried out to understand the colony formation potential. The protein expression for Bcl2 and p53 were assessed using western blotting. Results: The ability of TQ to overcome CDDP-induced drug resistance with the help of TQ in SKOV-3 cell lines. The minimum inhibition for SKOV-3 was 3 μM for CDDP and 14 μM for TQ. For the resistant SKOV3, the minimum inhibition was 6 μM for CDDP and 14 μM for TQ. The apoptotic bodies, mitochondrial membrane, nuclear condensation, and nuclear fragmentation were the observed morphological changes. The colony formation assay revealed reducing in the formation of clones. The protein expressions displayed modifications in the levels of p53 and Bcl-2 in both cell lines. Conclusion: TQ enhances apoptosis in SKOV-3 cells and is effective against the cells resistant to CDDP. This indicates a major application of TQ in recurrent OvCa that are resistant to CDDP.