Objective To determine whether diffusion kurtosis imaging (DKI) is effective in monitoring tumor response to neoadjuvant chemotherapy in patients with osteosarcoma. Materials and Methods Twenty-nine osteosarcoma patients (20 men and 9 women; mean age, 17.6 ± 7.8 years) who had undergone magnetic resonance imaging (MRI) and DKI before and after neoadjuvant chemotherapy were included. Tumor volume, apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and change ratio (ΔX) between pre- and post-treatment were calculated. Based on histologic response, the patients were divided into those with good response (≥ 90% necrosis, n = 12) and those with poor response (< 90% necrosis, n = 17). Several MRI parameters between the groups were compared using Student's t test. The correlation between image indexes and tumor necrosis was determined using Pearson's correlation, and diagnostic performance was compared using receiver operating characteristic curves. Results In good responders, MD post , ADC post , and MK post values were significantly higher than in poor responders ( p < 0.001, p < 0.001, and p = 0.042, respectively). The ΔMD and ΔADC were also significantly higher in good responders than in poor responders ( p < 0.001 and p = 0.01, respectively). However, no significant difference was observed in ΔMK ( p = 0.092). MD post and ΔMD showed high correlations with tumor necrosis rate ( r = 0.669 and r = 0.622, respectively), and MD post had higher diagnostic performance than ADC post ( p = 0.037) and MK post ( p = 0.011). Similarly, ΔMD also showed higher diagnostic performance than ΔADC ( p = 0.033) and ΔMK ( p = 0.037). Conclusion MD is a promising biomarker for monitoring tumor response to preoperative chemotherapy in patients with osteosarcoma.