BACKGROUND This study was conducted to assess if statin intake is associated with clinical parameters of periodontitis and matrix metalloproteinase (MMP) levels in gingival crevicular fluid (GCF) of nondiabetic and diabetic patients. METHODS We first determined the effect of simvastatin on MMP expression in mononuclear cells. We then recruited 117 nondiabetic and diabetic patients, who all had periodontitis and took or did not take statin, and measured periodontal probing depth (PPD) and clinical attachment level (CAL), and collected gingival crevicular fluid (GCF) to quantify MMPs. RESULTS The in vitro studies showed that simvastatin potently inhibited the expression of MMP-1, -8, and -9 upregulated by lipopolysaccharide (LPS) and high glucose in mononuclear cells. The patient study showed that, after adjusting for age and smoking status, PPD in diabetic patients on statin was significantly less than that in diabetic patients not on statin. MMP-1 level in GCF of nondiabetic and diabetic patients on statin was lower than that of nondiabetic and diabetic patients not on statin, respectively. No difference was found for MMP-8 and -9 levels in GCF. CONCLUSION Statin intake is associated with reduced PPD in diabetic patients and MMP-1 level in GCF in either nondiabetic or diabetic patients.