Background: The prevalence of periodontitis is significantly higher among people with poorly controlled diabetes mellitus (DM). The current study aimed to correlate the possible relation of stress in patients with chronic periodontitis as well as DM. Materials and methods: A total of 60 individuals were recruited in the age range of 35 to 50 years. Patients were divided into three groups which include 20 each: group I: chronic periodontitis with diabetic mellitus; group II: chronic periodontitis without DM; and group III: systemically and periodontally healthy individuals. Psychological assessment and biochemical analysis were carried out in all the patients. Results: Mean clinical attachment level (CAL) in group I was 6.21 mm, group II was 5.40 mm, and group III was 0.00 mm (healthy periodontium). Group I recorded highest mean cortisol levels of 22.55, which was significantly higher as compared with group III, which presented a mean cortisol level of 12.72. Mean cortisol level in group II was 15.70, which was marginally higher than in group II. Individual cortisol levels were relatively constant in group II (minimum 14 and maximum 18). Group III presented a skewed individual cortisol levels (minimum 8.78 and maximum 17.31), whereas group I presented a significantly high individual cortisol levels (minimum 16 and maximum 25.5). Group III presented least mean prostate symptom score (PSS) of 6.75, group II 18.55, and group III 24.90. Conclusion: There seems to be a strong correlation between periodontal destruction, DM stress, and serum cortisol levels. Clinical significance: Psychosocial stress influences the course and progression of periodontitis and should be addressed before and during treatment.