Objective To assess the effectiveness of the Gasdermin D C-terminal fragment （GSDMD-CT） as a novel plasma biomarker for the clinical diagnosis of sepsis. Methods Between July 2021 and November 2024， 245 patients from Tangshan Gongren Hospital were enrolled in this study. In accordance with the diagnostic criteria for sepsis and the systemic inflammatory response syndrome （SIRS）， patient samples were classified into the sepsis group and the SIRS group. Meanwhile， healthy individuals were selected as the healthy control （HC） group. Sepsis patients were further categorized into the Gram-positive bacterial group， the Gram-negative bacterial group， and the fungal group based on the type of pathogen infection. The levels of GSDMD-CT， C-reactive protein （CRP）， and procalcitonin （PCT） were measured in all subjects. Nonparametric tests were employed to compare the differences in various indices among different groups. The diagnostic value of GSDMD-CT in sepsis was evaluated by constructing the receiver operating characteristic （ROC） curve. Spearman's correlation analysis was used to examine the relationships among GSDMD-CT， CRP， and PCT. Results The plasma GSDMD-CT levels in the sepsis group 23.02（16.71， 33.01） pg/mL and in the SIRS group 16.52（11.26， 22.22） pg/mL were significantly higher than those in the healthy control group 7.02（4.42， 11.43） pg/mL （U = -10.175， -7.890， P < 0.001）. Moreover， the plasma GSDMD-CT levels in the sepsis group were significantly higher than those in the SIRS group （U = -2.941， P < 0.05）. In the Gram-positive bacterial group， the Gram-negative bacterial group， and the fungal group， the GSDMD-CT levels were 23.01（17.16，27.51）pg/mL， 23.41（16.78，35.50） pg/mL， and 16.29 （14.53，56.27） pg/mL， respectively. When compared with the healthy control group， the GSDMD-CT levels in these three groups were all significantly higher （P < 0.05）. However， there were no significant differences in GSDMD-CT levels among these three groups （P > 0.05）. The area under the curve （AUC） of plasma GSDMD-CT for diagnosing sepsis was 0.881 （95％ confidence interval： 0.833 ~ 0.929）， with a Youden index （YI） of 0.695， a sensitivity of 85.0％， and a specificity of 84.5％. Spearman correlation analysis indicated a weak correlation between GSDMD-CT and C-reactive protein （CRP） （r = 0.32， P < 0.001） and a positive correlation between GSDMD-CT and procalcitonin （PCT） （r = 0.65， P < 0.001）. Conclusion GSDMD-CT exhibits significant clinical value in the diagnosis of sepsis and holds great potential as a biomarker in the diagnostic process of sepsis.