The purpose of this study to evaluate the efficacy and safety of methotrexate (MTX) nanoparticle in paediatric patients with inflammatory bowel disease (IBD). The paediatric patients with moderate to severe IBD were enrolled in randomized, open-label clinical study. All eligible presents randomized in two groups. One group is treated with MTX nanoparticle (15 mg/week) while other groups were received azathioprine (AZA) (2 mg/kg/day). The nanoparticle was synthesized according to the procedure previously described. The erythrocyte sedimentation rate, Creactive protein, aspartate aminotransferase, alanine transaminase and disease activity score were used to determine the remission. Total 28 patients were enrolled in the study and randomized into two arms. After 12 weeks of therapy, the mean PCDAI for control and treatment groups were 22.3 ± 2.14 and 16.8 ± 1.87, respectively. Similarly, the mean PUCAI for control and treatment groups were 24.3 ± 1.47 and 18.7 ± 1.92, respectively. At the end of 12 weeks, eight patients in the treatment and five patients in the control group achieved remission. Conclusion: As per our knowledge, our study is the first to evaluate the safety and efficacy of nanoparticle formulation in paediatric IBD patients. We conclude that the MTX nanoparticle safe and more effective as compared to the slandered formulations.