The main objective of the current trial was to investigate the impacts of tilapia diets supplemented with S-methylmethionine sulfonium chloride (MMSC) on the growth performance, feed efficiency, body analysis, blood biochemistry and regulation of myostatin (MSTN) and insulin-like growth factor-1 (IGF-1) genes of nile tilapia (Oreochromis niloticus). The experimental fish (n=180) weighing 22.4±0.17 g were allocated randomly into three equal groups in triplicate as follows; the control group received an un-supplemented diet; the other two groups received two different levels of MMSC (0.2 and 0.4 g/kg) for eight weeks. The obtained findings demonstrated that tilapia diets enriched with small dosages of MMSC considerably (P<0.05) enhanced all assessed growth performance and feed efficiency indicators when compared with the control group. When compared to the control group, tilapia meals supplemented with 0.2 g MMSC significantly (P<0.05 or 0.01) raised blood protein profile, particularly total protein and globulin levels. Contrarily, blood creatinine levels were significantly (P<0.01) reduced in the group of tilapia fed diets containing MMSC (0.2 or 0.4 g/kg) compared to the group without receiving any supplementation. Whereas, fish body analysis showed higher significant increases in crude protein and ether extract levels (P<0.01) as well as reduced ash content (P<0.05) in the fish group that received lower MMSC doses in comparison to other treated and control groups. In addition, MMSC dietary supplementation significantly downregulated the expression of MSTN and upregulated IGF-1 mRNA expression compared with the control group. Additionally, both dosages of MMSC supplementation modestly enhanced the intestinal villus histomorphometric score indices with observed tall, thick, and various broad tips in comparison to the control group. In conclusion, it could be recommended that fish diets supplemented with 0.2 g MMSC per kg diet may promote the growth and general health status of Nile Tilapia.