The current study was conducted to evaluate the effects of different combinations of four dietary plant meal protein treatments {Mix (lupine, sesame, and jojoba meal), Mix+ (Methionine and Lysine), Soy con. (concentrate)+ and Soy+)} for Tilapia zillii on growth performance, biochemical indicators, and histological changes for 60 days. The results indicated that the highest significant final weight was recorded in the (Mix +), followed by the control group. The food conversion ratio and survival rate were better in these groups. The results of the study revealed that haemoglobin levels  (Hb), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and mean cell volume (MCV) were  all significantly increased (except for the soy con+ group) between the initial and final blood samples from fish fed the commercial diet and various diets used in the experiment. Blood samples from fish given both commercial food and different diets showed considerably elevated biochemical markers, except glucose and cholesterol. The histological examination revealed that an increase in the length of villi and the number of goblet cells were recorded in the intestine of Tilapia zillii groups fed on  Mix and Mix+ groups, compared to the control group. Finally, when compared to fish meal, plant protein is the only simple, affordable, and easily accessible substitute for fishmeal.