Background: Tissue destruction associated with the progression of periodontal disease is caused by a cascade of host and microbial proteolytic enzymes. Host-derived matrix metalloproteinases (MMPs) play an important role in the degradation of the extracellular matrix. Leukolysin/membrane-type 6 (MT-6)/MMP-25, the latest member of the MT-MMP subgroup of the MMP family, is primarily expressed by neutrophils and involved in extracellular matrix turnover. Matrilysin-2/MMP-26 (endometase), a novel member of the matrilysin subgroup of the MMP family, can degrade the extracellular matrix, alpha 1-antitrypsin, and activate pro-MMP-9. Our study aimed to examine the levels, molecular forms, and degrees of activation of MMP-25 and MMP-26 in gingival crevicular fluid (GCF) from patients with different periodontal diseases.