Background Schizophrenia is a chronic psychosis marked by multiple bioenvironmental and immunological dysregulation with its intricate role in etiopathogenesis of periodontal disease remaining unclear. Hence, the aim of this study is to determine the association between periodontal disease and schizophrenia in relation with cortisol levels. Methods The study is in descriptive design comprised of 40 subjects randomly selected (20 schizophrenic patients as Group A and 20 healthy volunteers as group B). All the study participants underwent complete periodontal examination including scoring of gingival index (GI), plaque index (PI), Probing depths (PD) and clinical attachment loss (CAL). Salivary cortisol levels are estimated using ELISA. Link between schizophrenia and periodontal disease is described in relation to cortisol levels with elimination of other shared risk factors, such as tobacco smoking and xerostomia. Results Significant higher values of periodontal parameters are observed in Group A with schizophrenic patients (GI 2.467 ± 0.528; PI 2.402 ± 0.526; PD 2.854 ± 0.865; CAL 1.726 ± 3.096) than Group B with healthy subjects (GI 0.355 ± 0.561; PI 0.475 ± 0.678; PD 1.493 ± 0.744; CAL 0.108 ± 0.254). However, cortisol levels are lower in schizophrenic group (0.190 ± 0.059) than non-schizophrenic group (0.590 ± 0.228) ruling out the possible role of cortisol in periodontal disease severity associated with schizophrenic patients. Conclusion Findings of this study, provides ground evidence for consideration of schizophrenia as a risk factor for periodontitis and demands greater emphasis on management of schizophrenic patients in dental setting similar to other comorbid disorders such as diabetes mellitus and also incorporating periodontal care measures in the clinical guidelines for schizophrenia management.