Background Postmenopausal women are at an increased risk of developing periodontitis due to hormonal changes affecting oral health. Interleukin-8 (IL-8) is a pro-inflammatory cytokine involved in the pathogenesis of periodontitis, and calcium plays a crucial role in bone metabolism and periodontal health. This study aims to evaluate and compare the salivary levels of IL-8 and calcium in postmenopausal females with and without periodontitis. Materials and Methods A total of 60 postmenopausal women were enrolled in this study, divided into two groups: 30 with periodontitis (Group A) and 30 without periodontitis (Group B). Unstimulated saliva samples were collected from all participants. IL-8 levels were measured using an enzyme-linked immunosorbent assay (ELISA), and calcium levels were determined using an automated biochemical analyzer. Statistical analysis was performed using the t-test and Pearson correlation coefficient. Results The mean salivary IL-8 levels in Group A were significantly higher (45.3 ± 10.4 pg/mL) compared to Group B (25.7 ± 6.8 pg/mL) (p < 0.01). Similarly, the mean salivary calcium levels in Group A were significantly lower (3.2 ± 0.8 mg/dL) compared to Group B (4.5 ± 1.0 mg/dL) (p < 0.01). A significant negative correlation was observed between salivary IL-8 and calcium levels (r = -0.54, p < 0.05). Conclusion Postmenopausal women with periodontitis exhibit higher salivary IL-8 and lower calcium levels compared to those without periodontitis. These findings suggest that salivary IL-8 and calcium levels could serve as potential biomarkers for the early detection and management of periodontitis in postmenopausal females.