Objective: To analyze the predictive value of dynamic platelet changes combined with D-dimer for the 28-day mortality risk in critically ill patients. Methods: A retrospective analysis was conducted on the clinical data of 500 critically ill patients admitted to the intensive care unit (ICU) of Shapingba District People’s Hospital in Chongqing from August 2023 to August 2025. Data on the maximum relative decrease in platelet count within 72 hours of admission and peak D-dimer levels were collected to analyze their correlation. Patients were divided into a death group (171 cases) and a non-death group (329 cases) based on 28-day all-cause mortality. Confounding factors were adjusted for to confirm whether the maximum relative decrease in platelet count within 72 hours and peak D-dimer levels were independent risk factors for 28-day mortality in critically ill patients. Based on the confirmation, the optimal cut-off values for both were analyzed, and a dual-parameter rapid judgment table was constructed, followed by performance testing and value analysis. Results: The maximum decrease in platelet count within 72 hours and peak D-dimer levels in the 500 patients showed a moderate correlation (r = 0.551, p = 0.012). Multivariate logistic regression analysis revealed that age, serum lactate, APACHE II score, SOFA score, maximum decrease in platelet count within 72 hours, and peak D-dimer levels were independent risk factors for 28-day mortality in critically ill patients (p < 0.05). ROC curve analysis indicated that the optimal cut-off values for predicting 28-day mortality in critically ill patients were 20% for the maximum decrease in platelet count and 5 mg/L for peak D-dimer levels. The dual-parameter rapid judgment table constructed based on these values demonstrated good discrimination (AUROC = 0.852, 95% CI: 0.811–0.883) when tested using the Bootstrap method. The assessment time for 30 patients using the dual-parameter rapid judgment table was (41.05 ± 8.37) seconds, and the predicted 28-day mortality showed good consistency with actual mortality (Kappa value = 0.726, p < 0.05). Clinical retrospective analysis revealed that the use of the dual-parameter rapid judgment table could potentially avoid a mortality rate of 16.96%. Conclusion: The maximum relative decrease in platelet count within 72 hours and peak D-dimer levels are closely related to the 28-day mortality risk in critically ill patients. The dual-parameter rapid judgment table constructed by combining these two factors requires less assessment time and has high application value in predicting the 28-day mortality risk in critically ill patients, contributing to a reduction in mortality.