Antimicrobial peptides of the epithelium play a significant role in the innate immune response in the oral cavity, which is constantly exposed to microbes. Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disease which is related to periodontal disease. To date, little is known about expressions of antimicrobial peptides in gingival epithelia of diabetics. Our aim was to examine the expression and localization of human beta-defensins (hBD)-2 and -3 and cathelicidin (hCAP18/LL-37) in diabetic subjects suffering from generalized periodontitis (GP). Gingival tissue sections were collected from three subject groups: 14 T2DM subjects with GP (T2DM+GP), 11 systemically healthy GP patients (GP), and 13 systemically and periodontally healthy subjects (control). Surgical incisions targeted the sulcular epithelium and/or the bottom of the selected periodontal pocket. Tissue specimens were fixed in paraformaldehyde and embedded in paraffin blocks. Immunohistochemistry stainings were performed for cytokeratin19, hBD-2, hBD-3 and hCAP18/LL-37. Stainings were examined under light microscope with 40× magnification. Results were statistically evaluated by the t-test. In controls, hBD-2 was localized at the superficial layers of the gingival epithelium, hBD-3 and hCAP18/LL-37 were at the basal layers, whereas in subjects with periodontitis both defensins were visible at all epithelial layers. hBD-2 was detected in the nucleus and cytoplasm, while hBD-3 and hCAP18/LL-37 were detected only in the cytoplasm of the cells. Expressions of hBD-2 (p=0.005), hBD-3 (p=0.007), and hCAP18/LL-37 (p=0.002) were elevated in subjects with T2DM+GP in comparison to controls. No statistically significant difference was found in the expression of hBD-2, -3, and hCAP18/LL-37 between the GP group and the control or T2DM+GP groups. Gingival antimicrobial peptides are overexpressed in T2DM. This outcome can be part of impaired immune response in diabetics, and underlying factors and mechanisms need to be elucidated.