Purpose: Cathepsin-K is an enzyme involved in bone metabolism. This feature may make it important both for natural teeth and dental implants. The aims of the present study were to comparatively analyze cathepsin-K levels in gingival crevicular fluid (GCF) and peri-implant sulcus fluid (PISF) and to determine whether GCF and PISF cathepsin-K profiles reflect the clinical periodontal/peri-implant status. Materials and Methods: Clinical parameters (probing depth, Gingival Index, Plaque Index, and bleeding on probing) were recorded, and GCF/PISF samples were obtained from natural teeth (group T) and dental implants (group I), which were divided into groups based on health (clinically healthy, gingivitis/peri-implant mucositis, and periodontitis/peri-implantitis). Cathepsin-K activity was determined with a commercially available cathepsin-K activity assay kit (BioVision). Results: Sixty natural teeth and 68 dental implants were examined. Teeth with periodontitis (group T-3) showed significantly higher total cathepsin-K activity (10.39 units) than teeth with gingivitis (group T-2, 1.71 units) and healthy teeth (group T-1, 1.90 units). The difference in cathepsin-K activity between groups T-2 and T-1 was not significant. Implants with peri-implantitis (group I-3) had higher total enzyme activity (10.26 units) than healthy implants (group I-1) (3.44 units). Although the difference between clinical parameters was not significant, group I-3 had higher cathepsin-K levels than group I-2 (4.74 units). When natural teeth (T-1, T-2, T-3) were compared to implants (I-1, I-2, I-3), no significant differences were observed for cathepsin-K levels. Conclusion: More cathepsin-K activity was clearly observed with inflammatory periodontal and peri-implant destruction. The highest cathepsin-K levels detected in GCF and PISF samples, obtained from sites with periodontitis and peri-implantitis, suggests the potential involvement of cathespin-K in increased bone metabolism around natural teeth and dental implants. Keywords: cathepsin-K, dental implants, gingival crevicular fluid, natural teeth, peri-implant sulcus fluid