The impact of dietary lysozyme (LZ) supplementation on the growth and laying performance was investigated over 4 weeks of growing and 6 weeks of laying periods in two different plumage color (white and brown-feathered) Japanese quail varieties. For each variety, 240 birds were randomly assigned into four groups with four replicates for each group. The first group (control) was fed a basal non-supplemented diet (BD). Whereas the 2nd, 3rd, and 4th received the BD supplemented with commercial LZ (CLZ) at 100 mg/kg diet, and natural LZ (NLZ) at 100 and 200 mg/kg diet, respectively. The main findings included significant increases in body weights and gains in the white-feathered quails supplemented with NLZ1 compared to the control and NLZ2. However, there were no significant differences in the case of brown-feathered quails in all LZ supplementations. Moreover, the different dietary LZ lowered FI in both quails with the lowest intake observed in the brown-feathered quails. Accordingly, enhanced FCR was reported in the CLZ groups for both quail varieties and in NLZ1 and NLZ2 for the white-feathered and brown-feathered quails, respectively. In both quail varieties, the NLZ2 significantly lowered serum creatinine and urea and increased albumen and globulin levels compared with other groups. Histologically, the best hepatic histological features were found in both quail’ varieties fed the NLZ1-supplemented diet. Accompanying LZ-induced modulations in the expression levels of GHR, IGF-1, leptin, CCK, FAS, and ACC genes in both quail varieties were reported. Besides, both quail varieties in NLZ1& NLZ2 supplementation exhibited significant increases in hen day egg production, egg weight, egg mass, and hatchability percentages along with differences in external and internal egg qualities compared with LZ-free diet or CLZ. Therefore, NLZ could be used as an effective feed supplement to enhance the growth and egg performance of Japanese quail with caution being drawn to the supplementation dose about quail variety.