The aim of this study was to reveal the effects of yeast culture replacing fish meal (FM) or chicken meal (CM) on the growth performance, serum biochemical indexes, intestinal digestive enzyme activities, hepatic antioxidant, and hepatic and intestinal histology of bullfrog (Lithobates catesbeianus). The basal diet contained 100 g/kg FM and 100 g/kg CM, and then yeast culture was used to decrease FM or CM level to 75 and 50 g/kg with yeast culture inclusion of 32 and 64 g/kg, respectively, resulting in five groups of isonitrogenous diets (control, FM75, FM50, CM75, and CM50). A total of 450 bullfrogs (45.5 ± 0.4 g initial weight) were fed the five diets for 50 days. (1) The FM50 group presented significantly lower weight gain, condition factor, hind leg index, and higher feed conversion ratio than the control group, while the other three groups of FM75, CM75, and CM50 showed no significant difference in growth performance when compared to the control group. (2) The serum triglyceride content of FM50 group was significantly lower, while the alkaline phosphatase activity was significantly higher than those of the control group. The serum total cholesterol levels were significantly lower in the CM50 group compared to the control group. (3) In intestinal digestive enzyme activities, the trypsin and α‐amylase activities in the CM75 and CM50 groups, the trypsin activity in the FM75 group, and lipase activity in the CM50 group were all significantly higher than those in the other groups. (4) The replacement of 50% FM with yeast culture (FM50 and CM50 groups) promoted the total antioxidant capacity in the liver, but compared to the control group, the intestinal villi height and muscularis propria thickness in the FM50 group were significantly lower. There was no difference (P > 0.05) in liver histology among all the groups. In conclusion, in a basal diet containing 100 g/kg FM and 100 g/kg CM, 32.0 and 64.0 g/kg yeast cultures could successfully replace 25% of dietary FM and 50% of dietary CM without negative effects on the growth performance, serum biochemical indexes, and hepatic and intestinal health of bullfrogs.