This study evaluated the subgingival proteome of parents with periodontitis and their offspring, thereby assessing signatures of periodontal disease. Forty participants were allocated into four groups (n = 10 per group): parents with periodontitis (PP) and their offspring (CP), and control parents (PC) and their offspring (CC). Periodontal clinical parameters were assessed. Gingival crevicular fluid (GCF) and subgingival biofilm were collected from the same sites. Proteome from GCF were investigated by liquid chromatography-tandem mass spectrometry with data-independent acquisition (DIA-PASEF).