Corn is the main energy source in most poultry feed. Due to rapid climate change, corn production cannot keep up with the demand for food and industrial applications. This necessitated the search for alternatives, such as agro-industrial by-products like mango seed kernel, which is a good source of carbohydrates and protein and can wholly or partly replace corn. The purpose of this study was to investigate the effect of partial replacement of yellow corn (YC) with soaked mango seed kernel (SMSK) on productive and reproductive performance, egg quality, blood biochemistry, hematological parameters, and antioxidants status of local laying hens. A total of 120 local Gimmizah breeds (108 females and 12 males) at 32 weeks of age were randomly assigned to four dietary treatments with three replicates (9 hens + 1 male per replicate). The treatments were YC replaced by SMSK at 0, 10, 15, and 20% levels in the hen diets for 12 weeks. Replacing YC with SMSK increased egg production, weight and number of eggs, and egg mass, and improved feed conversion ratio, but feed intake was not affected. Replacement of yellow corn with SMSK did not affect egg quality parameters. The hens in the SMSK 10% and SMSK 15% groups had the highest fertility, hatchability, post-hatch chick weight, and number followed by those in the SMSK 20% group. Groups given varying levels of SMSK had the lowest rate of embryonic mortality. Carcass weight and dressing percentage were positively affected by the 10% and 15% SMSK diet, except for the heart, pancreas, and spleen. Hematological indices were not influenced by dietary SMSK except for higher platelets in the SMSK 20% group. Total protein, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels were similar among treatments. In SMSK groups, serum total cholesterol, triglycerides, and malondialdehyde levels decreased significantly, whereas IgG and catalase levels increased. These findings indicated that SMSK up to 20% could be considered a successful nutritional and health approach and can be partially substituted for YC with no adverse impact on the productive, reproductive and physiological performance of laying hens.