Objectives The aim of this study was to analyze the mRNA and protein expression of adiponectin, leptin, visfatin, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels in periodontitis and peri-implantitis sites in systemically healthy individuals and to investigate the influence of the presence of current periodontitis on their expression levels in peri-implantitis sites. Materials and methods Soft tissue biopsy samples were collected from 60 systemically healthy patients [15 periodontally healthy patients (group I), 16 patients with periodontitis (group II), 15 patients with peri-implantitis (group III), and 14 patients with peri-implantitis and periodontitis (group IV)]; mRNA expression levels of adiponectin, leptin, visfatin, TNF-alpha, and IL-6 were measured by quantitative real-time PCR; and their protein levels were assessed by immunohistochemistry. Results The mRNA expression levels of all biomarkers were significantly higher for group II compared to group I, while significantly higher levels of leptin, TNF-alpha, and IL-6 were observed in group III in comparison with group I. Group II exhibited significantly higher mRNA expression of adiponectin and TNF-alpha than group III. Group IV showed significantly higher expression levels of adiponectin, leptin, TNF-alpha, and IL-6 compared to group III. Regarding the expression of protein levels, which was estimated through quantification of the histoscore, both groups II and III presented higher H-scores than group I for all biomarkers except leptin. Conclusions The presence of current periodontitis may enhance expression levels of adiponectin, leptin, TNF-alpha, and IL-6 in peri-implant soft tissue.