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.