Atypical antidepressant mirtazapine (MIR) is primarily used to treat major depressive disorder. It has not been clarified whether cardiovascular uncertainties and mechanisms of action emerge as problems during the use of mirtazapine. Cisplatin (CIS) is an effective anti-cancer medication used to treat a variety of human malignancies. There were four groups of 32 Wistar albino male rats in all. Rats were split into 4 groups at random. 1. Control Group, 2. CIS Group, 3. MIR Group, 4. MIR+CIS Group. On the 15th day of the study, ECG, heart rate, and blood pressure were determined. Histopathological and biochemical analyses were carried out on cardiac and vascular tissue samples. Comparing the CIS group to the other groups, blood pressure was considerably lower in the CIS group (p<0.05). In vascular tissue examination, catalase and superoxide dismutase levels were substantially higher in the control, MIR, and MIR+CIS groups, similar to those of the myocardium, compared to the CIS group (p<0.05). While the CIS group had the highest malondialdehyde level, it was much lower in all other groups in both myocardial and vascular tissue (p<0.05). It was observed that the congestion persisted, but the interstitial edema's intensity was much less severe in the MIR+CIS group than in the CIS group (p=0.009). We sought to clarify the function of the oxidative system, tissue-level histological alterations, the possibility that mirtazapine protects against CIS cardiotoxicity, and the role of MIR in cardio-oncology in this study. In this study, we demonstrated the possible protective effect of MIR in CIS-mediated cardiotoxicity and its antioxidant effect mechanism.