Objective <p>To evaluate the diagnostic utility of T-helper type 2 (Th2) cytokines, specifically Interleukin-4 (IL-4), IL-5, IL-10, and IL-13, in distinguishing different stages of pulpitis and their combined performance in clinical diagnosis.</p> Methods <p>A total of 161 participants were enrolled and categorized into normal pulp (NP, <i>n</i> = 45), reversible pulpitis (RP, <i>n</i> = 75), and symptomatic irreversible pulpitis (IP, <i>n</i> = 41). Th2 cytokine levels in pulpal blood samples were measured using enzyme-linked immunosorbent assays (ELISA).</p> Results <p>Th2 cytokine levels (IL-4, IL-5, IL-10, and IL-13) were significantly elevated in pulpitis cases compared to normal pulp, with the highest concentrations observed in symptomatic IP. Diagnostic analysis showed that IL-4 and IL-13 had the highest diagnostic accuracy for distinguishing pulpitis (both RP and IP) from normal pulp, with AUCs of 0.91, and perfect specificity (100%). IL-5 demonstrated the best balance between sensitivity (68%) and specificity (97%) for differentiating IP from NP (AUC = 0.84). IL-13, though less effective overall, provided moderate accuracy (AUC = 0.63) for distinguishing RP from NP. Additionally, the combined diagnostic model of all four cytokines achieved high AUCs, particularly in distinguishing irreversible pulpitis from normal pulp (AUC = 0.94) and irreversible pulpitis from reversible pulpitis (AUC = 0.90).</p> Conclusions <p>Th2 cytokines, especially IL-4, IL-5, and IL-13, are effective biomarkers for identifying different stages of pulpitis. Their elevated levels, particularly in irreversible pulpitis, provide strong diagnostic accuracy. Combined cytokine analysis enhances diagnostic precision, making Th2 cytokine profiling a valuable tool for assessing pulpitis severity.</p>