Introduction:In this regard, the purpose of this research was to study the combined effects of autolyzed baker's yeast (Saccharomyces cerevisiae) and edible mushroom powder (Agaricus bispirus) on growth parameters, digestive enzymesactivity and intestinal histology of rainbow trout fingerlings (Oncorhynchus mykiss). Materials & methods:This research was conducted in one of the Urmia Rainbow Trout Breeding Farms (Golden Pond Fish Breeding).This research was evaluated in the form of 4 experimental treatments each with 4 replicates. Rainbow trout with an average weight of 15 ± 2 g were fed with experimental diets including: control group (treatment 1), autolyzed yeast at the rate of 2% of the diet (treatment 2), edible mushroom powder at the rate of 1% diet (Treatment 3) and 2% autolyzed yeast combination together with 1% edible mushroom powder (Treatment 4) for 10 weeks. At the end of the rearing period, growth indices, nutritional efficiency, digestive enzyme activity (protease, amylase and lipase) and intestinal morphology indices (villi length, muscle layer thickness and number of goblet cells) were measured and evaluated. Results:The results showed that the addition of 2% autolyzed yeast and 1% edible mushroom powder could not make a significant difference in the indicators of final weight, weight obtained, food conversion ratio, activity of digestive enzymes protease, amylase, intestinal lipase and villi length indicators as well as the thickness of the muscle layer and the number of goblet cells in the small intestine of fish compared to the control group (P>0.05). Also, the results showed that the simultaneous adding of 2% autolyzed yeast and 1% edible mushroom powder in the diet of rainbow trout could significantly enhanced growth indicators, nutritional efficiency, digestive enzymes activity and intestinal morphology indicators in comparison with other experimental groups (P<0.05). Conclusion: According to the results of this research, adding of 2% autolyzed yeast (Saccharomyces cerevisiae) along with 1% edible mushroom powder (Agaricus bispirus) as a prebiotic is recommended to improve growth indicators, digestive tract function and feeding efficiency.