Objective To develop a quantitative scoring system based on conventional ultrasonographic semantic features and to evaluate its diagnostic value for diffuse thyroid disease (DTD). Methods A total of 185 patients with clinically suspected DTD were prospectively enrolled from Shanghai Fourth People’s Hospital Affiliated to Tongji University and Naval Medical Center of Naval Medical University between Mar. 2024 and Jan. 2025. Based on the salivary gland ultrasonographic scoring method for Sjögren’s syndrome, a quantitative scoring system of ultrasonographic semantic features of DTD was constructed, comprising 8 core indicators: volume and shape, capsular integrity, echogenicity, homogeneity, nodules, linear hyperechogenicity, calcifications, and vascular pattern, with a total score ranging from 0 to 19. Two senior ultrasound physicians (with ≥5 years of experience) independently performed double-blind scoring according to this system. To assess intra-observer reliability, 30% of the cases (n=56) were randomly selected and re-scored after a 2-week interval. Both inter-observer and intra-observer consistency were assessed using the intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the scoring system. Multivariate binary logistic regression was applied to identify independent predictive factors among the ultrasonographic semantic features for discriminating DTD. Results Based on laboratory tests (thyroid function, thyroid peroxidase antibody, thyroglobulin antibody, and thyroid stimulating hormone receptor antibody), clinical history, and imaging follow-up, 128 of the 185 (69.19%) suspected DTD patients were confirmed as DTD, and 57 (30.81%) as non-DTD. The median score of the quantitative ultrasonographic semantic feature scoring system in the DTD group was significantly higher than that in the non-DTD group (9 vs 4, P＜0.001). Inter-observer and intra-observer agreements were excellent (ICC=0.97 and 0.96, respectively). ROC curve analysis showed that the quantitative ultrasonographic semantic feature scoring system demonstrated excellent diagnostic performance for DTD, with an area under the ROC curve of 0.91 (95% confidence interval 0.87-0.96). At the optimal cut-off value of 5.5, the sensitivity was 93% and the specificity was 87%. Multivariate regression revealed that glandular homogeneity and vascular score were independent predictors for DTD. Conclusion The quantitative scoring system based on conventional thyroid ultrasonographic semantic features shows good diagnostic performance and high reproducibility for DTD. It may contribute to the development of an intelligent structured reporting system for thyroid ultrasound, showing promise as an auxiliary tool for objective and quantitative ultrasonographic diagnosis of diffuse thyroid disease.