Background <p>Graves' ophthalmopathy (GO) is a challenging autoimmune manifestation of Graves' disease, whose management relies on accurate assessment of inflammatory activity in the extraocular muscles (EOMs). The Clinical Activity Score (CAS), the current gold standard for assessing disease activity, is based on subjective clinical signs. Consequently, objective imaging biomarkers are urgently needed as a complement orbital ^99mTc-DTPA SPECT/CT imaging holds potential, but its quantitative methodology lacks standardization. This study aimed to evaluate the utility of four SPECT/CT-derived quantitative indices for quantifying EOM inflammatory activity in GO.</p> Results <p>Group Differences: EOM uptake values for all four indices were significantly higher in the active GO group than in both the inactive and control groups (all <i>P</i> ＜ 0.001). No significant differences were found between the inactive and control groups.</p> Clinical Correlation <p>All quantitative parameters showed significant positive correlations with the CAS (all <i>p</i> ＜ 0.001). </p> Diagnostic Performance <p>ROC curve analysis confirmed that all indices effectively differentiated active from inactive GO, with SUV_mean yielding the superior diagnostic efficacy (AUC = 0.887). </p> Conclusions <p>In summary, this study confirms that quantitative indices from orbital ^99mTc-DTPA SPECT/CT, particularly SUV_mean-3D, effectively quantify EOMs inflammatory activity in GO. Parameters derived using CT-based 3D VOI delineation (SUV_mean-3D and SUV_max-3D) demonstrated superior reliability over traditional methods. Among all indices, SUV_mean-3D demonstrated superior diagnostic efficacy (AUC = 0.887) for differentiating active from inactive disease. These indices provide an objective tool for quantifying GO severity and monitoring disease changes during patient follow-up. This capability is vital for monitoring treatment response, guiding therapeutic decisions, and serving as a potential endpoint in clinical trials.</p>