This study aimed to clarify the influence of chewing on human β-defensin 2 (hBD-2) and secretory immunoglobulin A (SIgA) expression levels. We included 15 healthy males with no missing teeth (mean age, 25.5±2.5years). Subjects were instructed to chew a piece of gum for 30min. Saliva and skin-extraction samples were collected before and after chewing for 15 and 30min. hBD-2 and SIgA concentrations in the samples were determined using enzyme-linked immunosorbent assay (ELISA). hBD-2 and SIgA expression levels before and after chewing were analyzed using the Mann-Whitney U test, following the Friedman test. The significance level was 0.05. The hBD-2 level in skin-extraction samples was significantly different before (99.4±17.3pg/mL) and after chewing for 30min (142±23.0pg/mL). The SIgA level in skin-extraction samples was also significantly different before (2.39±0.25μg/mL) and after chewing for 30min (3.61±0.33μg/mL). No significant difference was noted in either hBD-2 or SIgA secretion rate in saliva between before and after chewing. Chewing gum for 30min increased hBD-2 and SIgA expression levels in skin. Moreover, chewing gum could influence the secretion pattern of these two biomolecules on skin, but not in saliva. Copyright © 2018 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.