This study aimed to investigate incorporated silk warm by-product feeds as an unconventional source of protein for the Nile tilapia, Oreochromis niloticus fingerlings diets, and its impact on their growth performance and physiological status. In this study, 160 monosex Nile tilapia fingerlings with an average live weight of 2.6 ± 0.04g were used. They were divided into four groups and distributed among 16 aquariums, with 10 fries per aquarium. The aim was to investigate the impacts of including silkworm by-product feeds (SWBF) as an unconventional source of protein in the Nile tilapia fingerlings' diets on their growth performance, feed utilization, apparent protein digestibility, blood parameters, body composition, energy retention percentages (ER%), protein productive value percentages (PPV%), and intestinal villi absorptive capacity. Four levels (0, 10, 20, and 30%) of SWBF were incorporated into the experimental diets to partially or completely replace a portion of the soybean meal. The feeding trial was extended for 84 days, and fish were hand-fed at a rate of 3%. The results indicated that Oreochromis niloticus fingerlings fed on a diet containing 10% silk-warm by-products showed improvements in growth, and survival ratio, with a reduction in the number of dead fish and mortality rate. Moreover, dry matter and crude protein intakes increased. Both feed conversion & protein efficiency ratio and apparent protein digestibility were significantly improved. Blood contents which include albumin, globulin, albumin: globulin ratio, red blood cell count (RBC's), ASAT, ALAT, and urea were significantly (P< 0.05) affected, and values of ASAT, ALAT, and urea were decreased. The body composition of dry matter and villi length of the duodenum, ileum, and rectum significantly (P< 0.05) increased. From the results obtained in our study, it is clear that 10% silkworm by-products can be successfully used as an unconventional source for rearing the Nile tilapia fingerlings, significantly affecting their growth and survival. Additionally, the energy retention and protein productive value improved, with no adverse effects on the apparent protein digestibility, blood constituents, body composition, energy retention percentages, protein productive value (PPV), and intestinal villi absorptive capacity of the Nile tilapia fingerlings.