Periodontal disease is a widespread chronic condition linked to systemic illnesses such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Despite its global burden, population-specific studies on its risk factors remain limited, particularly in Central and Eastern Europe. The SANA-biome Project is a cross-sectional, community-based study designed to investigate the biological and social determinants of periodontal disease in Romania, a country with disproportionately high oral disease rates and minimal microbiome data. This protocol will integrate metagenomic, proteomic, and metabolomic data of the oral microbiome from saliva and dental calculus samples with detailed sociodemographic and lifestyle data collected through a structured 44-question survey. This study is grounded in two complementary frameworks: the IMPEDE model, which conceptualizes inflammation as both a driver and a consequence of microbial dysbiosis, and Ecosocial Theory, which situates disease within social and structural contexts. Our aims are as follows: (1) to identify lifestyle and behavioral predictors of periodontal disease; (2) to characterize the oral microbiome in individuals with and without periodontal disease; and (3) to evaluate the predictive value of combined microbial and sociodemographic features using statistical and machine learning approaches. Power calculations based on pilot data indicate a target enrollment of 120 participants. This integrative approach will help disentangle the complex interplay between microbiological and structural determinants of periodontal disease and inform culturally relevant prevention strategies. By focusing on an underrepresented population, this work contributes to a more equitable and interdisciplinary model of oral health research and supports the development of future precision public health interventions.