It is widely known that the use of medicinal plants and probiotics as feed additives has a positive effect on growth, non-specific immune system, and resistance to diseases in aquaculture. This study examines the effects of dietary supplementation with sage (Salvia officinalis) and myrtle (Myrtus communis), alone or in combination with a probiotic mixture (PM) on growth, intestine microflora and histology, some antioxidant enzymes activities in the muscle tissues of rainbow trout (Oncorhynchus mykiss) and disease resistance against Vibrio anguillarum. For this purpose, fish were fed with a control diet of 1% sage, 1% myrtle, 1.1% probiotic mixture, 1% sage +1.1% PM and 1% myrtle+1.1% PM supplemented diets for 60 days. At the end of the trial, the fish fed the diets supplemented with myrtle and sage + PM showed a positive effect on feed conversion ratio. According to the histological assessment, the villi length, villi width and goblet cell numbers in the intestines of fish in all groups increased compared to the control. Superoxide dismutase activity in the muscles of fish in the PM group was higher than the fish in the other groups (p<0.05). The malondialdehyde activity was unaffected with the exception of the fish in the sage group (p<0.05). The lactic acid bacteria count in the intestines increased in fish fed the sage + PM (p<0.05). Fish fed the diets supplemented with sage + probiotic mixture, probiotic mixture, myrtle + probiotic mixture, and myrtle saw a significant reduction in mortality (0-32.5%) due to V. anguillarum compared to the control (63.2%) (p<0.05). In conclusion, the use of probiotics, sage and myrtle in combination as a feed supplement showed a positive effect on the growth performance, intestinal microflora and histology, and antioxidant enzymes activities and disease resistance in rainbow trout.