Objective(s):The present study aims to evaluate the efficacy of administered diosgenin (DG) which has anti-oxidant and anti-inflammatory effects, on alveolar bone loss (ABL) and apoptosis in diabetic rats with periodontitis.Materials and Methods:Forty male Wistar albino rats (n=40) were divided into five subgroups; control (non-ligated), periodontitis (P), diabetes mellitus (DM), P+DM, and P+DM+DG. To stimulate experimental periodontitis, a ligature was embedded at the gingival margin of the lower first molars for each rat, and diabetes was induced by streptozotocin (STZ) for DM groups. Then, DG (96 mg/kg daily) was performed on the P+DM+DG group by oral gavage for 29 days. At day 30, all animals were euthanized and the distance from the cement-enamel junction to the alveolar bone margin was measured using cone-beam computed tomography as ABL. In addition, immunohistochemical analyses were used to evaluate the expression levels of alkaline phosphatase (ALP), osteocalcin (OCN), bone morphogenetic protein 2 (BMP-2), receptor activator of NF-κB ligand (RANKL), collagen type I (Col-1), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax).Results:Induction of periodontitis and diabetes significantly increased ABL (P<0.05). DG administration significantly reduced ABL, expression of RANKL and Bax, and enhanced the expression of ALP, OCN, BMP-2, Bcl-2, and Col-1 in the P+DM+DG group compared with the P+DM group (P<0.05).Conclusion:It is revealed that DG considerably enhanced bone formation and contributed to periodontal healing in this experimental study performed in diabetic rats.