Simple Summary In this study, the effects of cadmium (Cd) on renal function and bone metabolism of laying hens were investigated. Results indicated that supplementation with Cd can damage renal function, induce oxidative stress in the kidney, disrupt the body’s calcium balance and hormone secretion, and negatively affect bone metabolism of laying hens. The results demonstrated that chronic exposure to Cd could induce renal dysfunction and bone damage in laying hens. Abstract This study was conducted to evaluate the toxic effects of cadmium (Cd) on the kidney function and bone development in laying hens. A total of 480 Hy-line laying hens aged 38 weeks were randomly allocated into five treatments, each of which included six replicates of 16 birds. The concentrations of Cd in the diets of the five groups were 0.47, 7.58, 15.56, 30.55, and 60.67 mg/kg. Results showed that serum calcium (Ca) levels decreased significantly in the 60.67 mg Cd/kg diet group ( p < 0.05). The activities of serum alkaline phosphatase (ALP) and bone ALP (BALP) decreased significantly in the 15.56, 30.55 and 60.67 mg Cd/kg diet groups ( p < 0.05). The levels of parathyroid hormone (PTH) increased significantly in the 30.55 and 60.67 mg Cd/kg diet groups, and the estradiol (E2), 1,25-(OH)2-D3 and calcitonin (CT) decreased significantly with the increase of dietary Cd supplementation ( p < 0.05). Histological results presented enlargements of renal tubules and tubular fibrosis in the kidney and decreased trabecular bone in the tibia. Tartrate-resistant acidic phosphatase (TRAP) staining results of tibia showed that osteoclast was significantly increased at the relatively high dose of dietary Cd ( p < 0.05). In addition, the renal function indicators of blood urea nitrogen (BUN), urea acid (UA), and creatinine were significantly increased in Cd supplemented groups compared with the control group ( p < 0.05). Low dose Cd exposure induced antioxidant defenses accompanying the increase in activities of catalase (CAT), glutathione peroxidase (GSH-Px), and the levels of glutathione (GSH) in renal tissue. At the same time, with the increased Cd levels, the activities of CAT, GSH-Px decreased significantly, and the level of malondialdehyde (MDA) increased significantly ( p < 0.05). The activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase decreased significantly in the relatively high levels of dietary Cd ( p < 0.05). These results suggest that Cd can damage renal function and induce disorders in bone metabolism of laying hens.