Background: Periodontal disease (PD) is a chronic inflammatory condition linked to systemic immunologic and metabolic alterations. This study evaluated associations between PD and three routinely measured blood biomarkers—white blood cell (WBC) count, serum albumin, and mean corpuscular hemoglobin concentration (MCHC)—using data from 4669 adults aged ≥30 years in the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Methods: PD was defined dichotomously according to the Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP) surveillance criteria. All analyses incorporated NHANES sampling weights, strata, and primary sampling units. Weighted descriptive statistics compared characteristics by PD status. Stepwise survey-weighted logistic regression examined associations between biomarkers and PD, adjusting for sociodemographic, behavioral, and health-related confounders. Restricted cubic splines assessed nonlinearity, and biomarker effects were additionally scaled per standard deviation (SD). Results: Higher WBC counts (OR = 1.08; 95% CI: 1.04–1.11) and higher MCHC values (OR = 1.14; 95% CI: 1.06–1.22) were positively associated with PD, whereas serum albumin showed an inverse association (OR = 0.76; 95% CI: 0.62–0.93). Spline models demonstrated significant nonlinear components for all biomarkers, and SD-scaled estimates confirmed consistent gradients. Conclusions: These findings support links between periodontal inflammation and systemic hematologic alterations. Longitudinal studies are needed to clarify underlying mechanisms.