In this study, we evaluated the effects of two different regimens of dietary supplementation with grape seed extract (GSE) based on serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and osteocalcin (OC) in experimental periodontitis. The investigation was performed at the Department of Animal Experimentation at Erciyes University, Kayseri, Turkey, from May 2011 to June 2011. Experimental periodontitis was induced by placing 5.0 silk sutures around the maxillary first molars. Twenty-seven adult male wistar rats were divided into four study groups as follows: Healthy control (HC; N = 7); Ligature only (LO; N = 6); Ligature-induced periodontitis plus GSE 50 mg/kg (GSE 50; N = 8); Ligature-induced periodontitis plus GSE 100 mg/kg (GSE 100; N = 6). GSE administration was performed for 14 days-following induction of experimental periodontitis. On day 15, serum samples were obtained and rats were sacrificed Serum samples were analyzed for TAS, TOS, OSI and OC. Defleshed jaws were analyzed morphometrically for alveolar bone loss. The results showed that placing 5.0 silk sutures around maxillary first molars resulted in statistically significant bone loss compared to the HC group (P < 0.05). None of the GSE administrated groups showed evidence that GSE was effective in preventing ligature-induced alveolar bone loss. The GSE 100 and GSE 50 groups had a significantly higher TAS compared to the HC group. No significant differences were seen in TOS, OSI and OC levels. As a whole, GSE administration does not seem to influence TAS, TOS and OC. The lack of a therapeutic benefit of GSE in this study is difficult to explain, and further studies are required to fully assess-the potential role of GSE in periodontal treatment.