The current study was conducted to evaluate the synergistic effect of Artemisia dracunculus , Myrtus communis and Ducrosiaanethifolia extract residues on performance, egg quality, blood biochemistry parameters, ileal bacterial enumeration, intestinal histology, immunological responses, antioxidant indices of blood and liver, and fatty liver indices in laying hens. In this study, 180 Hy-line W-36 Leghorn hens of 52 weeks of age were randomly assigned among 9 treatments with 4 cages of 5 birds each. Dietary treatments consisted of positive control (basal diet with 20 ppm vitamin E), negative control (NC, basal diet without vitamin E or residues), NC with 50 g/kg Myrtus residues, NC with 50 g/kg tarragon residues, NC with 50 g/kg D. anethifolia residues, NC with 25 g/kg Myrtus and 25 g/kg D. anethifolia residues, NC with 25 g/kg Tarragon and 25 g/kg D. anethifolia residues, NC with 25 g/kg Myrtus and 25 g/kg tarragon residues and NC with 16.6 g/kg Myrtus , 16.6 g/kg tarragon and 16.6 g/kg D. anethifolia residues, that fed during a 80 d feeding trial including 10 days for adaptation period and 70 days as main recording period. Performance parameters including feed intake, feed conversion ratio, egg production percentage, egg weight, egg mass and also egg quality were calculated on d 35, and 70 of experiment. To investigate the immunological response, sheep red blood cells (SRBC) were injected in twice with 10 d interval; thereby, hens were bled 6 and 12 d after the first and second injection, respectively. Moreover, Newcastle disease virus was injected and then sera were taken 6 d after injection. In addition, differential leukocyte counts were evaluated at the end of experiment. At the end of experiment, two birds of each cage were exsanguinated to evaluate the relative weight of liver, spleen as well as pancreas, and also to sample ileal content and jejunal morphology. The results of this experiment showed that administration of the mixture of Myrtus and D. anethifolia -residues resulted in increased villus height to crypt depth ratio (P 0.05), improved antibody titer against SRBC (P=0.07) and Newcastle disease virus (P 0.05) and spleen weight (P 0.001), caused a decrease in heterophil to lymphocyte ratio (P 0.05) and a reduction in hepatic and serum MDA concentration. Moreover, dietary supplementation of the mixture of tarragon and D. anethifolia residues led to a decrease in the ileal Escherichia coli enumeration (P 0.01), an improvement in performance indices like egg production percentage (P 0.001), egg production efficiency (P 0.0001), feed conversion ratio (P 0.001) and egg shell thickness (P 0.01). Additionally tarragon residues resulted in decreased serum triglyceride (P 0.05) and cholesterol (P 0.0001) concentration. In general, results indicate that the best immunological and histological responses were observed when 50 g/kg of Myrtus and D. anethifolia -residues were supplemented in