Over the years there has been research on how to improve fish yield. This study investigated the effects of variegated grasshopper meal (Zonocerous variegatus) on growth performance, nutrient utilization, and gene expressions in juvenile Clarias gariepinus (African catfish). The variegated grasshopper meal diets (VGDMs) were incorporated with the other feed ingredients at 25% (VGDM1), 50% (VGDM2), 75% (VGDM2), and 100% (VGDM3) diets while the remaining group served as control. Growth performance, nutrient utilization, and gene expression study were evaluated. The mRNA expression of Growth hormone (GH), Heat Shock Protein (HSP70), Melatonin (MEL 1C), tumour necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) were investigated in the liver and muscle of C. gariepinus fed with varying doses of grasshopper meals (VGDMs) using reverse transcriptase–polymerase chain reaction. There were significant (p>0.05) variations in all parameters in all the treatments. There was a significant upregulation (p<0.05) in the gene expression of GH, HSP70, MEL 1C, and TNF-α in VGDM1 compared to control in both tissue groups. In addition, there was significant downregulation (p<0.05) in interleukin 1 (IL-1β) gene expression in liver VGDM2. This study suggests that dietary variations involving VGMD have the potential to boost growth and improve the immune responses of this fish species.