Background: Periodontitis, a chronic inflammatory disease, has been associated with various systemic conditions and diseases. Biomarkers have high potential to quantify the extent of its spread and its association with other systemic diseases. This study aimed to potentiate the link between periodontitis and cardiovascular diseases and to assess the levels of inflammatory mediators such as interleukin-6 (IL-6) and C-reactive protein (CRP). Aim: The aim of this study is to examine the circulating levels of CRP and IL-6 as inflammatory indicators associated with cardiovascular diseases among individuals with periodontitis. Methodology: A total of 20 individuals, both men and women above the age of 30–50 years, were included. The individuals were divided into two groups of healthy controls (group I, n = 10) and grade III, stage C periodontitis (group II, n = 10). Gingival tissue samples from inflamed regions were collected while performing mechanical debridement from periodontitis patients using Gracey curettes (Hu-Friedy®, Chicago, IL, USA). Healthy tissue obtained while performing surgical crown lengthening procedure using modified Widman flap from tissues without any clinical signs of inflammation were collected and quantized for enzyme-linked immunosorbent assay (ELISA). The immunological assay and the clinical parameters such as gingival index (GI), plaque index (PI), probing pocket depth (PPD), and clinical attachment levels (CAL) were assessed among the two groups. Tissue samples obtained from individuals were estimated using EliKine's ELISA kit for IL-6 and CRP. Statistical analysis was done, and the results were evaluated for normality. According to the data, it followed a parametric distribution and independent t-test was done with (p < 0.05) being statistically significant. Result: The mean CRP levels were compared; group II showed statistical significance compared to group I, with mean ± SD of 27.06 ± 1.55 in group II and 21.84 ± 2.20 in group I (p < 0.05). Similarly, group II had a higher mean ± SD of IL-6 level than group I, ranging from 173 ± 6.19 pg/mL in group II to 133 ± 4.17 pg/mL in group I. Differences in mean values of IL-6 and CRP between the two groups were considered statistically significant according to an independent t-test (p < 0.05). Conclusion: Currently, a variety of clinical parameters are employed almost exclusively in the diagnosis of periodontitis. Clinical assessments are also the basis for the most dependable prognostic indications that may lead to diagnosing future disease progression. If reliable systemic biomarkers for periodontal disease were accessible as a diagnostic test, they may be very helpful. Periodontitis results in higher systemic levels of CRP and IL-6. These elevated inflammatory factors may increase inflammatory activity, presenting an increasing risk for cardiovascular events.