Aquaponics is recognized as an innovative and environmentally friendly production system. The aim of this study is to examine the effect of feeding insect meal (H. illucens), insect frass and hydroponic by-products (vegetative parts of tomato and cucumber plants, as well as low quality, non-marketable cucumbers and tomato fruits) as a replacement of fishmeal on the protein metabolism performance of common carp (Cyprinus carpio) teared in a laboratory closed-loop aquaponic system (CLA). A total of 297 C. carpio individuals were obtained from a local fish hatchery and were distributed in 9 CLA systems. In the hydroponic part of the system, 108 L. sativa individuals were placed in the hydroponic baskets. Three diets (3 replicates/dietary treatment) were formulated, the Control diet (C) containing 15% of fishmeal, the H. illucens diet (B), were the fishmeal protein of the control diet was replaced at 50% by H. illucens meal and the plant residues (F) diet were the fishmeal protein of the control diet was replaced at 50% by a mix of H. illucens meal, H. illucens frass and hydroponic by-products at a 2:1:1 ratio. Growth performance indicators of common carp showed no statistically significant differences across the three dietary treatments (p>0.05) during the 45 days of the experimental period. All 9 CLA systems effectively cultivated lettuce with optimal root-to-shoot ratios. Immunoblotting analysis was employed to evaluate the expression of proteins involved in cellular signaling, such as p38 MAPK, Bad and Bcl-2, and Na+‐K+‐ATPase, in the kidney of C. carpio under the three dietary regimes. According to the results, both the activation of p38 MAPK (Figure 1) and the Na+‐K+‐ATPase levels were significantly suppressed in response to the diets B and F. Previous studies have indicated that MAPKs are considered among the downstream members that are activated through the Na+‐K+‐ATPase. Moreover, both B and F diets led to reduction of the Bad/Bcl-2 ratio, a crucial indicator in the death or survival of the cells. These results indicate that the experimental diets may exert beneficial effects regarding the cellular response of C. carpio.