In the current study, the possible synergistic properties of resveratrol (Res) and two‐strain probiotics (Pro; Lactobacillus acidophilus and Bifidobacterium bifidum) on growth performance, innate immune responses, antioxidant defence and disease resistance against Yersinia ruckeri were assayed in rainbow trout. Accordingly, fish (10.42 ± 0.26 g) were fed with a basal diet as control and diets supplemented with R1 (400 mg/kg Res), R2 (800 mg/kg Res), P1 (0.5 g/kg Pro), P2 (1 g/kg Pro), R1P1 (400 mg/kg Res + 0.5 g/kg Pro) and R2P2 (800 mg/kg Res + 1g/kg Pro) for 8 weeks. The final weight, weight gain and feed conversion rate significantly improved in fish fed the P1, P2, R1P1 and R2P2 (p < .05), after 8 weeks. Diets containing R1P1 and R2P2 significantly elevated the total leucocyte count, and percentages of monocyte and neutrophil at the end of the 8th week (p < .05). Serum complement activity, lysozyme activity and bactericidal activity (BA) of fish fed the diets containing P1, P2, R1P1 and R2P2 were higher than the control group. Oral administration of R2P2 remarkably increased mucus immune parameters (lysozyme, BA, alkaline phosphatase and total immunoglobulin) (p < .05). Moreover, the highest activity of catalase, superoxide dismutase and glutathione peroxidase, and the survival rate were recorded in the R2P2 group. In conclusion, R2P2 remarkably elevated growth performance, innate immune and antioxidant responses, and disease resistance in rainbow trout.