Recently, cold atmospheric pressure plasmas (CAP) have emerged as a promising oncotherapeutic modality, through physical and chemical effects. Here, for the first time, A2780 CP and SKOV-3 cells, relevant to ovarian cancer and GCs as normal ovarian cells were evaluated through CAP directly, indirectly, and concomitant modality of plasma activated medium (PAM) with common drugs to overcome chemotherapy resistance in ovarian cancer. Our results confirm the high potential and the stronger selectivity of PAM in comparison to CAP for the selected cell lines and selectivity mechanism was related to the pH and concentration of H2O2, NO2-, and NO3- reactive species in the plasma stimulated medium. Compared to the combination of common carboplatin (CAR) and paclitaxel (PTX) chemotherapy treatments, the PAM-based treatment is very promising for ovarian cancer treatment. Our data verify that PAM alone and in combination with carboplatin sensitizes cancer cells to carboplatin, inhibits the SOD1 gene, and selectively induces apoptosis accompanied with high expression of p53, Bax, and activation of Caspase-3. Collectively, our observations revealed PAM treatment is an innovative and emerging technology for the future combination or multimodal ovarian cancer oncotherapy.