Assays of salivary biomarkers for diagnosis are gaining popularity in pediatric diseases due to their non-invasive nature. Our pilot project aims to evaluate the utility of salivary leucine-rich-alpha-2-glycoprotein (LRG) in the diagnosis of pediatric acute appendicitis (AA).We prospectively recruited 34 patients, aged between 4 and 16 years, admitted with acute abdominal pain suspicious of appendicitis. The patients' demography, clinical characteristics, laboratory investigations, imaging examination results, operative findings, and discharge diagnoses were recorded. We compared the diagnostic performance of the patients' total white counts, neutrophil percentages, C-reactive protein, and saliva LRG levels. Saliva samples were obtained using the SalivaBio Children's Swab and LRG levels were quantified using a commercially available LRG enzyme-linked immunosorbent assay (ELISA) kit. IRB approval was obtained.Seventeen patients had a confirmed diagnosis of appendicitis on histology. Another 17 were confirmed not to have appendicitis after a minimum of 24 h of hospitalization, with further verification via telephone interview 2 weeks later. The median levels of saliva LRG were elevated in patients with AA as compared to those without (P = 0.008). At a cutoff of LRG 0.33 ng/μg, we obtained a diagnostic specificity of 100% and sensitivity of 35.3%.Our proof-of-concept study demonstrated the diagnostic potential of saliva LRG for appendicitis in children. The distinct advantage of saliva LRG assays is that the procedure is simple, pain-free, and requires no specialized skill. Further study with a larger cohort is needed to verify our results.