Cerebral adrenoleukodystrophy (CALD) is an X-linked inflammatory demyelinating disorder leading to death within a few years. CALD can be halted by hematopoietic stem cell transplantation (HSCT) or gene therapy (GT) when applied at early disease stages. Currently, eligibility for treatment is determined by MRI-based brain lesion Loes scoring. However, this grading system poorly reflects later disease stages or atypical lesion patterns. As such, there is a need for alternative biomarkers to help with treatment decisions. We recently identified inflammatory activity and CALD progression being reflected by blood-derived neurofilament light chain protein (NfL), indicative of axonal injury, and glial fibrillary acidic protein (GFAP), reflecting astrocyte activation/damage. Here we investigated how pre-treatment blood biomarker levels associate with treatment outcome and assessed rescue of neuronal injury and glial activation over time. Using longitudinal plasma samples from CALD children and single-molecule Simoa assay, we identified that elevated baseline NfL levels associated with worse treatment outcome. One month after HSCT or GT, significant further elevation of blood NfL and GFAP indicated neurotoxicity of the myeloablative conditioning that might be of concern for more advanced patients. In CALD patients with pre-treatment NfL levels <100 pg/ml, subsequent NfL levels decreased to less than baseline after one year with stabilization of the disease course. Plasma GFAP revealed prolonged amelioration of astrogliosis, indicating sustained astrocyte activation one year post treatment. We conclude that biomarkers indicative for neuroinflammation could complement current decision-making especially in more advanced CALD children, where thorough evaluation of the benefits and drawbacks of treatment becomes essential.