In the present study, potential ameliorative effects of dietary ginger (GN) were investigated on antioxidant and immune responses of rainbow trout (Oncorhynchus mykiss) during oxytetracycline (OX) administration. As a 2 × 3 factorial design, the fish were orally treated with OX (a daily dose of 100 mg/kg) and GN (either 10 or 20 g/kg diet) for 10 days. Then, blood samples were taken from each treatment to monitor plasma lysozyme, complement (ACH50), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and reduced glutathione (GSH), malondialdehyde (MDA), total immunoglobulin (Ig) and globulin levels. OX treatment significantly decreased SOD (30%), GPx, (10%) and lysozyme (23%) activities, and GSH (19%) levels; however, it increased GST (16%) activity and MDA (28%) levels. Ten grams GN per kg levels significantly decreased SOD (35%), CAT (13%), GST (20%) and MDA (30%), but increased GSH (30%), lysozyme (48%) and globulin (16%). Twenty grams GN per kg diet significantly decreased SOD (26%) and MDA (17%), but increased lysozyme (31%) levels. Interaction effects of dietary GN and OX were observed on plasma MDA and GPx levels, as 10 g GN per kg diet prevented the OTC-induced changes in these parameters. Moreover, 20 g GN per kg diet prevented the OX-induced change in GPx activity and mitigated the MDA elevation by 20%. It is concluded that GN administration at 10 g/kg diet is beneficial in mitigating oxidative stress and immunosuppression of rainbow trout during OX administration. © 2020 John Wiley & Sons Ltd