Neuronal ceroid lipofuscinosis type 6 (CLN6) is a fatal, neurodegenerative disorder demonstrating progressive gliosis/neuronal loss and vision impairment. Onset occurs in childhood leading to cognitive/motor decline and premature death. No approved pharmacological treatments yet halt disease progression. Flupirtine is a neuroprotective agent with anti‑apoptotic properties. Hypothesis: The flupirtine benzyl carbamate derivative mitigates CLN6‑associated pathology by reducing neuroinflammation/apoptosis and normalizing dysregulated gene expression. Oral flupirtine benzyl carbamate derivative/vehicle was administered to Cln6nclf mice ages 4-28 weeks. Immunofluorescence measures of astrocytic activation (GFAP), neuronal survival (NeuN) and accumulation of subunit C of ATP synthase (SubC) were determined. Retinal whole mounts were examined for levels of SubC/GFAP/hodopsin and cone photoreceptor markers. TUNEL assay quantified apoptotic cell death in brain/retinal tissues. Behavioral testing included tail suspension, open field and novel object recognition, allowing characterization of motor coordination/cognitive performance. Microarray analysis of RNA profiles identified dysregulated gene expression in Cln6nclf mouse brain associated with cell death and inflammation. Extent of normalization of expression after giving the benzyl carbamate derivative is discussed. The drug significantly attenuated astrocytosis-affected areas in cortex/hippocampus in Cln6nclf mouse brain with reduced GFAP‐positivity,decrease in SubC-positive puncta versus vehicle‑treated male/female mice. NeuN immunoreactivity increased confirming neuronal preservation in 28‑week‑old treated male/ female mice. TUNEL‐positive cell numbers were reduced in brain/retina demonstrating anti‑apoptotic effect in both sexes. No significant restoration of rhodopsin protein expression/cone photoreceptor densities in retina occurred suggesting more direct delivery may be warranted. Upregulated proinflammatory cytokine genes were normalized to wild‑type levels by microarray profiling. Behavioral assessments demonstrated improvement reducing hyperactivity, spasticity and visual acuity in treated male mice, with females only exhibiting significantly diminished spasticity. Results strongly suggest that the flupirtine benzyl carbamate derivative ameliorates neuroinflammation/neuronal survival in both sexes. Improved behavioral and motor/cognitive outcomes were more substantial in Cln6nclf male mice supporting potential as a disease‑modifying therapy.