We investigated the effects of caffeic acid phenethyl ester (CAPE) and low-dose doxycycline (LDD) on sclerostin and bone morphogenic protein (BMP)-2 expression in experimental periodontitis. We used male rats in groups as follows: control group (C), periodontitis + CAPE group (PC), periodontitis + LDD group (PD), periodontitis + LDD + CAPE group (PCD) and periodontitis group (P). We administered 10 mu mol/kg/day CAPE by an intraperitoneal (i.p.) injection and 10 mg/kg/day LDD by oral gavage. Histopathological changes among groups were evaluated and compared. Sclerostin and BMP-2 expression was analyzed using immunohistochemistry. LDD and/or CAPE treatment ameliorated pathology. The highest sclerostin and lowest BMP-2 expressions were found in P group. Group PC exhibited the highest BMP-2 expression scores and the most significant improvement among the treatment groups. The lowest sclerostin expression was observed in the PD group. We found that preventing sclerostin activity may be a useful treatment alternative for bone resorption, especially in cases of periodontitis and peri-implantitis. We found that CAPE and/or LDD may act as anti-sclerostin agents.