Objective: To investigate the expression and diagnostic value of D-dimer, CRP, and IL-6 in children with Mycoplasma pneumonia. Methods: A total of 100 children diagnosed with Mycoplasma pneumonia from the pediatric department of the First Affiliated Hospital of Shaoyang University, admitted between November 2023 and June 2024, were selected for the study. According to the severity of the condition, they were divided into two groups: a mild group (50 cases) and a severe group (50 cases). After treatment, they were further divided into an effective group (63 cases) and a non-effective group (37 cases) based on the treatment outcomes, to compare their diagnostic values. Results: The levels of D-dimer, CRP, IL-6, length of hospital stay, fever resolution time, cough resolution time, and the time for lung rales to disappear were higher in the severe group than in the mild group (P < 0.05). The levels of D-dimer, CRP, and IL-6 in the non-effective group were higher than those in the effective group (P < 0.05). In this study, using pathological results as the “gold standard,” it was found that the positive detection rate for the combined detection of D-dimer, CRP, and IL-6 was higher than the detection rate for each of D-dimer, CRP, and IL-6 alone, suggesting that the combined diagnosis had a higher positive detection rate (P < 0.05). Compared with D-dimer, CRP, and IL-6, the combined sensitivity, specificity, and accuracy were all higher (P < 0.05). Conclusion: D-dimer, CRP, and IL-6 are closely related to Mycoplasma pneumonia in children and can serve as auxiliary diagnostic tools for Mycoplasma pneumonia in children, offering significant value.