Periodontitis is a common chronic inflammatory disease characterized by alveolar bone loss. The high polyphenol content in cocoa pod husk (Theobroma cacao L) has the potential to influence bone metabolism and contribute to the inhibition of bone resorption. The aim of this study was to analyze the anti-osteoclastogenesis potential of cocoa pod husk (Theobroma cacao L.) in both in silico and in vivo study. An analysis of the anti-osteoclastogenesis potential of T. cacao bioactive compounds was conducted using molecular docking simulations. Thirty male Wistar rats (Rattus novergicus) were randomly assigned to control negative groups (placebo gel), control positive groups (2% doxycycline gel), and treatment groups (10% cocoa pod husk (CPH) extract gel), with measurements taken on days 7 and 14. Wistar rats were induced with 0.05 ml of P. gingivalis at a concentration of 2x109 CFU/ml intrasulcularly in the maxillary molar to achieved in periodontitis. The number of osteoclasts was observed by hematoxylin and eosin staining, the level of TNF-α was assessed by enzyme-linked immunosorbent assay, and the expression of RANKL was evaluated by immunohistochemical staining. Data were analyzed using One-way ANOVA to examine the differences between the groups. The in silico study showed that the catechin, epicatechin, quercetin, and procyanidin B2 had a strong binding affinity for TNF-α and RANKL. Administration of 10% CPH reduced the number of osteoclasts (p<0.05), TNF-α level on days 7 and 14 (p<0.05), and RANKL expression on day 7 (p<0.05) in experimental rats with periodontitis. Administering 10% CPH inhibited osteoclastogenesis in the experimental periodontitis rats.