The present study aimed to evaluate the effects of oleuropein on ligature-induced alveolar bone loss. In this respect, osteoblastic activity, osteoclastic activity, inflammatory markers, and apoptosis were evaluated.Oleuropein is a flavonoid, which has potent anti-inflammatory and bone-protective effects.Thirty-two Wistar rats were divided into four experimental groups as following: control (C, n = 8) group; periodontitis (P, n = 8) group; periodontitis and low-dose oleuropein group (12 mg/kg/day oleuropein, LDO group, n = 8); and periodontitis and high-dose oleuropein group (24 mg/kg/day oleuropein, HDO group, n = 8). Periodontitis was induced via ligatures. Study period was 14 days, and animals were sacrificed at end of this period. Mandibles were examined via a stereomicroscope and underwent histological procedures. Osteoblast, tartrate-resistant acid phosphatase (TRAP)-positive osteoclast, and inflammatory cell counts were determined in hematoxylin-eosin stained sections. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-4, the cluster of differentiation (CD)-68, cysteine-aspartic proteases-3 (Caspase 3), and B-cell lymphoma-2 (Bcl-2) expressions were evaluated via immunohistochemistry.Periodontitis group had highest alveolar bone loss, and these levels significantly decreased in LDO and HDO groups. Both 12 and 24 mg/kg oleuropein groups significantly increased osteoblast cell counts and decreased TRAP-positive osteoclast and inflammatory cell counts. BMP-4 and bcl-2 expressions were elevated in oleuropein groups while caspase-3 expressions decreased. iNOS and CD68 were higher in periodontitis group compared to control group, but there was no significant difference between other groups.Oleuropein successfully decreased alveolar bone loss as a result of decreased osteoclastic activity, inflammation, and apoptosis and increased osteoblastic activity.