The aim of this study was to evaluate the effects of host modulation therapy on periodontal and biochemical parameters. Sixteen rheumatoid arthritis patients newly scheduled for anti-tumour necrosis factor (TNF) therapy were screened for 30 days. Periodontal parameters (clinical attachment level, probing pocket depth, bleeding on probing, plaque index and gingival index) as well as salivary and gingival crevicular fluid (GCF), interleukin (IL)-1β, IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels of the patients were evaluated at baseline and on the 30th day of therapy. GCF volume, IL-1β and IL-8 levels (p = 0.007, p = 0.017 and p = 0.009, respectively) of the periodontitis patients significantly decreased. Although there was a decrease in all these parameters in healthy patients, it was below statistical significance. Salivary IL-8 and MCP-1 levels significantly decreased in periodontitis patients (p = 0.028 and p = 0.013, respectively), but IL-1β levels remained unchanged. These results suggest that TNF blockers may significantly modify host response in terms of biochemical parameters of the periodontium and may mask significant associations such as those reported between periodontitis and rheumatoid arthritis.