Objective To investigate the ponderal growth and survival post-chemotherapy of optic pathway glioma (OPG) in children with diencephalon syndrome (DS). Methods Six OPG patients with DS admitted from May 2018 to December 2020 were analyzed retrospectively. The median age of children was 13.5 (3 - 43) months. The median weight Pre-chemotherapy of children was 6.9(6-8) kg. None of the children gained weight prior to the OPG diagnosis, and all exhibited cachexia and extreme emaciation upon admission. The weight-for-age Z score (WAZ) was below -2 in all six patients pre-chemotherapy. The weight changes were dynamically monitored during chemotherapy, and WAZ was assessed at 1, 3, 6, 9 and 12 months post-chemotherapy. Repeated measures analysis of variance was used to compare the WAZ and survival at different time points after chemotherapy. Results The median follow-up time was 46(29-59) months. Visual acuity did not significantly improve in two children with anopsia after surgery or chemo-radiotherapy. Nystagmus, present in four patients at disease onset, resolved post-chemotherapy and one child had central precocity. After chemotherapy, one patient was lost to follow-up, and three experienced tumor progression, which was managed with maintenance chemotherapy to stabilize the disease. There were no fatalities.The weight of all children increased significantly compared with that prechemotherapy, and WAZ increased significantly with the extension of chemotherapy time (P<0.05). Conclusion In children with DS with OPG, postoperative chemotherapy can improve ocular symptoms and promote weight gain.