Hypertension is a risk factor for generalized periodontitis (GP) and chronic kidney diseases (CKD). However, the role of isolated systolic blood pressure as one of the major risks for these inflammatory diseases has not been explored. Very limited studies exist identifying the red-complex bacteria in association with the isolated systolic blood pressure. Hence, the main objective of this study was to assess the isolated systolic blood pressure and the red-complex bacteria along with the demographic variables, periodontal parameters, and renal parameters in patients with generalized periodontitis and chronic kidney disease. One hundred twenty participants (age 30–70 years) were divided into four groups—Group C: control (systemically and periodontally healthy subjects), Group GP: generalized periodontitis, Group CKD: subjects with CKD with good periodontal health, Group CKD + GP: subjects with both generalized periodontitis and CKD. Demographic variables and periodontal parameters were measured and recorded. Blood pressure measurements and a detailed history and renal parameters such as serum creatinine, eGFR, and fasting blood sugar were recorded. The red-complex bacteria (RCB) were assessed in the subgingival plaque samples of all four groups using RT-PCR. Older participants (above 50 years) showed worse periodontal scores in the CKD + GP group along with elevated isolated systolic blood pressure, higher serum creatinine, and fasting blood sugar. eGFR was significantly decreased compared to the other groups. Bacterial counts were higher in the GP + CKD group, suggesting that they may be at a higher risk for generalized periodontitis and chronic kidney disease. Isolated systolic blood pressure (ISBP) and RCB were significantly correlated with the renal and periodontal parameters. A log-linear relationship exists between periodontal disease, CKD, RCB, and isolated systolic hypertension levels.