Abstract Context: The C-reactive protein (CRP) is an acute-phase reactant protein that is produced in response to various inflammatory and noxious stimuli that include exposure to heat, traumatic conditions, varieties of infectious processes, and conditions of hypoxia. Estimation of CRP levels in serum samples helps in providing important information related to the diagnosis, monitoring, and treatment of inflammatory processes and various associated diseases. Materials and Methods: This prospective longitudinal study was designed to evaluate serum CRPs in subjects who were selected for study participation after fitting into inclusion criteria, which were as follows: a) study participants who were clinically diagnosed with chronic generalized periodontitis along with periodontal pocket depths of ≥5 mm and also radiographic alveolar bone loss; b) subjects within the age range of 35 to 55 years; and c) no smoking habit or use of tobacco in any other form. Results: Patients were assessed for clinical parameters such as gingival index, sulcular bleeding index, mean depth of periodontal pocket, and loss of clinical attachment. Blood was collected at required visits, and CRP was evaluated. Study evaluation periods were baseline (day 0), day 14 (2nd appointment), and day 45 (3rd appointment). Results: Statistically significant reductions in both clinical and serum CRP levels were obtained at subsequent appointments. Conclusion: This study has demonstrated and supported the evidence that serum CRPs act as a biomarker in determining the prognosis of chronic periodontitis patients after nonsurgical periodontal treatment.