Abstract Background: Timely diagnosis of periodontal disease is crucial for restoring healthy periodontal tissue and improving patients’ prognosis. There is a growing interest in using salivary biomarkers as a noninvasive screening tool for periodontal disease. This study aimed to investigate the diagnostic efficacy of two salivary biomarkers, lactate dehydrogenase (LDH) and total protein, for periodontal disease by assessing their sensitivity in relation to clinical periodontal parameters. Furthermore, the study aimed to explore the impact of systemic disease, age, and sex on the accuracy of these biomarkers in the diagnosis of periodontal health. Materials and methods: A total of 145 participants were categorized into three groups based on their basic periodontal examination index, with 20 in the periodontally healthy group, 50 in the gingivitis group, and 75 in the periodontitis group. Salivary LDH was measured using the rate of nicotinamide adenine dinucleotide (NADH) oxidation, to measure the kinetics of LDH activity, while total protein was measured using the Lowry method. Descriptive and analytical statistical analyses were performed to examine the associations between the variables and biomarkers. Results: The results of the study demonstrated that salivary LDH was 72% sensitive, while salivary total protein was 78% sensitive in correlation to clinical periodontal parameters. The accuracy of the test was not influenced by sex, but age had a significant effect on both biomarkers, particularly LDH. Systemic disease was another factor that significantly affected the accuracy of the test. Conclusions: Although salivary LDH and total protein show promise as biomarkers for screening periodontal disease, their interpretation may be impacted by age and systemic disease.