Background: Knowledge of typical medication use among patients with chronic periodontitis or destructive periodontal disease is limited. The aim of this study was to associate periodontitis severity with the use of different classes of medications. Methods: Patients (N = 12,631) who had medical, dental, and pharmaceutical coverage with a health maintenance organization and whose severity of destructive periodontal disease was diagnosed by a dentist or specialist were included in the study. The rate of drug use over 7 years was related to the severity of destructive periodontal disease by means of Poisson regression models. Results: Individuals with moderate to advanced periodontitis had significantly lower fill rates for the respiratory agents (antihistamines: -23%, 95% confidence interval [CI]: -10% to -34%; decongestants: -24%, 95% CI: -13% to -34%; and cough/cold medications: -12%, 95% CI: -3% to -21%) and anti-infective agents (antibiotics: -12%, 95% confidence interval: -6% to -18%; urinary anti-infectives: -36%, 95% CI: -6% to -56%; and topical antibiotics: -18%, 95% CI: -5% to -29%). Conclusions: More severe periodontitis was a marker for reduced medication use for allergies and infections. The associations between destructive periodontal disease, infections, allergies, and the hygiene hypothesis need further exploration.