In summary, the total phenylethanoid glycosides, isolated from C. deserticola, exhibited significant beneficial effects on postmenopausal osteoporosis of OVX rats, and the therapeutic potential in suppressing bone loss was mainly through stimulating bone formation and inhibiting bone resorption as well as improving the bone antioxidant system; the mechanisms may be related to RANKL/RANK/TRAF6-induced NF-κB activation and PI3K/AKT inactivation as well as c-Fos stimulation and NFAT2 suppression, and finally, the differentiation of osteoclast was inhibited. Here, FOS is linked to postmenopausal osteoporosis.