This study assessed the potential applicability of Moringa oleifera leaf meal (MO) and fermented Moringa oleifera leaf meal (FMO) as feed supplements for aquatic animals. Five experimental diets, including the basal diet (control), 2.2% and 4.4% MO-supplemented diets (MO2 and MO4), and 2.2% and 4.4% FMO-supplemented diets (FMO2 and FMO4), were prepared for feeding Megalobrama amblycephala juveniles. After the eight-week feeding trial, the growth performance, muscle nutritional composition, plasma and hepatic biochemistry indicators were measured. The results demonstrated that MO and FMO had no detrimental effects on the growth performance of M. amblycephala juveniles. The muscle crude protein, crude lipid, and total free amino acids contents were significantly enhanced in the FMO4 group (p < 0.05). The liver acetyl-CoA carboxylase α mRNA level was significantly increased and the lipoprotein lipase mRNA level was markedly reduced in the FMO4 group (p < 0.05). Therefore, the FMO4 group exhibited a significant increase in plasma low-density lipoprotein cholesterol and triglyceride levels (p < 0.05). Compared to the control group, total superoxide dismutase and catalase activities were significantly increased in the FMO4 group (p < 0.05). The FMO2 and FMO4 groups exhibited an anti-inflammatory response by inhibiting the expression levels of toll-like receptor 4, nuclear factor-kappa B, and tumor protein P53 mRNA (p < 0.05). In conclusion, the 4.4% FMO treatment increased muscle crude protein content, enhanced lipogenesis, and improved the hepatic antioxidant abilities of M. amblycephala juveniles, while 2.2% FMO and 4.4% FMO improved the liver anti-inflammatory capacities.