Background: Caged layer osteoporosis (CLO) is a common bone metabolic disease and is threatening the modern poultry industry. The objective of this study was to evaluate effects of total flavonoids of Rhizoma Drynariae (TFRD), a Chinese herbal extract, on bone health, egg quality and production performance in caged laying hens. Totals of 144 Lohmann pink-shell laying hens of 32-wk-old were randomly allocated to 4 groups (CON, LCD, TFRD1 and TFRD2, respectively). The CON group was fed a basal diet, the LCD group was fed a low calcium diet (LCD) and the TFRD1 and TFRD2 groups were fed LCD supplemented with 0.5 and 2.0 g/kg TFRD, respectively.Results: Supplying 2.0 g/kg TFRD produced protective effects on calcium deficiency-induced bone loss in caged laying hens, including reduced serum levels of alkaline phosphatase and tartrate resistant acid phosphatase activities (both P < 0.05) and osteocalcin content (P < 0.05), enhanced femur bone mineral density (P < 0.05), improved bone microarchitecture deterioration, down-regulated mRNA expressions of RANKL (P < 0.01) and up-regulated RUNX2 and OPG levels (both P < 0.01). Furthermore, compared to LCD group, 2.0 g/kg TFRD treatment had lower malondialdehyd levels (P < 0.01), and higher total antioxidant capacity (P < 0.05) and glutathione peroxidase (P < 0.05) activities, which contributed to the protective effects of bone loss. TFRD supplementation did not affect egg quality while 2.0 g/kg TFRD treatment improved laying rate (P < 0.05) and decreased feed conversion ratio (P < 0.05).Conclusions: These findings suggested that TFRD has beneficial effects on bone health and production performance in caged laying hens, which can be used for the prevention of CLO.