HE present investigation was designed to verify the effect of using Spirulina platensis (Sp) on growth performance, blood biochemical parameters, and expressions of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor1 (IGF-1), insulin-like growth factor 2 (IGF-2), and myostatin (MSTN) genes in Nile tilapia. A total of 96 fingerlings (12 ± 0.2 g) were randomly allocated into eight groups, each containing 12 fish, and fed diets containing 0%, 1% (10 g), 2% (20 g), and 3% (30 g) SP/kg for 8 weeks. Significant improvements in growth were observed in the 1% SP group, with the best feed conversion rate at 1.09. Biochemical parameters, including serum protein, globulin, liver enzymes (ALT and AST), cholesterol, and glucose concentrations, were analyzed using a spectrophotometer for calorimetric analysis. Higher serum protein and globulin levels were observed in the 1% SP group compared to the control. RT-PCR analysis indicated elevated GH expression in the brain and muscles, along with increased IGF-1 and IGF-2 levels observed in the liver and muscle tissues of the 1% SP group compared to the control and other treatments. However, there was a positive correlation between the 1% SP diet and enhanced MSTN mRNA levels in muscle tissues. Except for higher ether extract (EE) in the 2% SP treatment, there were no significant changes in fish survival or body composition. Overall, this study recommends utilizing 1% SP as a dietary supplement to improve growth, feed utilization, biochemical parameters, and growth-related gene expressions in Nile tilapia.