Background <p>Magnetic resonance imaging (MRI) radiomics has shown promise in glioma grading and isocitrate dehydrogenase (IDH) mutation prediction, but traditional whole-tumor approaches overlook intratumoral heterogeneity, limiting diagnostic accuracy and interpretability. This study aims to explore cellularity habitat-based MRI radiomics for precise grading and IDH mutation status prediction in adult-type diffuse glioma (ADG).</p> Methods <p>A total of 625 ADG patients were retrospectively collected. Whole-tumor volumes of interest (VOIs) were delineated on four conventional MRI sequences (T1WI, T2WI, T2-FLAIR, and CE-T1WI) and segmented into three cellularity habitats using apparent diffusion coefficient (ADC)-based K-means clustering: H₁ (low ADC), H₂ (medium ADC), and H₃ (high ADC). Radiomic features were extracted from individual and combined habitats, and predictive models were developed using a disentangled-learning-based multi-sequence fusion network (DMSFN). Performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE).</p> Results <p>The optimal habitats for ADG grading (Grade 2 vs. Grade 3 + 4, Grade 2 + 3 vs. Grade 4) and IDH prediction were H_1 + 2, H_1 + 2, and H_2 + 3, respectively. Combining T1WI, CE-T1WI, and T2-FLAIR sequences yielded the highest AUCs of 0.9360, 0.9605, and 0.8721 in the training set, and 0.8070, 0.8236, and 0.8180 in the independent test set. Shapley Additive exPlanation (SHAP) analysis identified key radiomic features contributing to model predictions, with CE-T1WI features consistently demonstrating high discriminative power.</p> Conclusions <p>Integrating ADC-derived cellularity habitats with MRI radiomics significantly improves the accuracy and biological interpretability of ADG grading and IDH mutation status prediction, offering a robust, non-invasive approach for glioma characterization.</p> Trial registration <p>Retrospectively registered.</p>