Manuka honey contains unique anti-microbial activity and is a premium product in the market. To verify its authenticity, two distinct markers, lepteridine and leptosperin derived from manuka nectar, have been identified in the honey by previous studies. A previous study has also found that manuka honey has displayed beneficial effects on bone, but it has been largely unknown as to what components have contributed to this skeletal action. In the current study, the honey’s authenticity markers, lepteridine and leptosperin, have been evaluated for their effects on bone cells in vitro. In mouse bone marrow cell cultures, both of the components mildly inhibited osteoclastogenesis as well as reducing the osteoclastogenic factors/markers levels: Dc-stamp, Nfatc1, cathepsin K and Trap. Since the metabolism of leptosperin leads to the production of syringic acid and methyl syringate, the effect of these metabolites on bone cells has also been investigated. It was found that methyl syringate, but not syringic acid, also inhibited osteoclastogenesis and is even more potent than its precursor leptosperin. The inhibition on osteoclasts by these honey components was confirmed in RAW264.7 cell cultures. Since some pro-inflammation cytokines are stimulatory to osteoclastogenesis and honey is known to contain anti-inflammatory activity, the effect of the honey components on the expression of the pro-inflammation cytokines was evaluated in cultured bone marrow cells. It was found that leptosperin partly and methyl syringate significantly reduced the expression of Il-1b, Il-6 and Tnfa. In osteoblastic MC3T3-E1 cell cultures, both leptosperin and methyl syringate at lower concentrations (0.01 to 1 µg/mL) mildly stimulated 3H-thymidine incorporation, an indication of increased cell proliferation. These results suggest that lepteridine, leptosperin and methyl syringate are the anabolic factors present in manuka honey conferring the beneficial skeletal effect.