Background: Cardiovascular diseases as well as periodontitis can be regarded as current epidemics and have become a social problem. Mean platelet volume (MPV) is a simple, routinely assessed biochemical parameter, which is becoming regarded as a new, independent risk factor of acute coronary syndromes and stroke. Aim: Assessment of a potential relationship between clinical indices of periodontal disease and MPV in relation to the presence of coronary artery disease (CAD) and chronic periodontitis. Methods: The study included 57 individuals aged from 50 to 65 years. Patients were divided into three groups. Group 1 consisted of 19 patients with previously diagnosed CAD and coexisting chronic periodontitis. Group 2 included 18 patients with diagnosed chronic periodontitis with excluded CAD. Group 3 was a control group and consisted of 20 healthy individuals without CAD or periodontitis. Results: Unsatisfactory oral hygiene defined by plaque index (PI) was observed in all patients. Mean PI was significantly higher in Groups 1 and 2 than in Group 3 (76.7% vs. 45.7%, p < 0.01). Mean bleeding index (BI) was significantly higher in Group 2 than in Groups 1 and 3 (46.4% vs. 29.8%, p < 0.05). Mean periodontal pocket depths (PD) (2.75 mm, 2.93 mm, 1.97 mm, respectively, p < 0.05, p < 0.01) and clinical attachment loss (CAL) were significantly higher in Groups 1 and 2 than in Group 3 (5.13 mm, 4.79 mm, 1.31 mm, respectively, p < 0.01). Mean WBC, fibrinogen and hsCRP were not significantly different among the examined groups (WBC 6.81 G/L vs. 6.71 G/L vs. 6.18 G/L, fibrinogen concentration 4.31 g/L vs. 3.94 g/L vs. 3.67 g/L; hsCRP concentration 4.08 mg/dL vs. 6.61 mg/dL vs. 4.33 mg/dL). In Group 1, MPV was significantly higher than in Group 3 (10.39 fL vs. 9.39 fL, p < 0.01). There was a weak, although significant, correlation between periodontal parameters and MPV and correlations between MPV and PD as well as CAL (MPV-PD: r = 0.45, p < 0.05; MPV-CAL: r = 0.42, p < 0.05). Conclusions: Chronic periodontitis in patients with CAD results in an increased MPV that may suggest increased platelet activity. This observation could indicate a potential pathophysiological link between chronic periodontitis and an increased risk of acute coronary syndromes.