Enteric neuropathy is increasingly recognised as a contributor to dysmotility and symptom burden in inflammatory bowel disease (IBD), yet therapies that protect or restore enteric neurons remain limited (Lakhan and Kirchgessner 2010). Krill oil (KO), rich in phospholipid-bound long chain n-3 fatty acids and antioxidant astaxanthin, has demonstrated neuroprotective actions in the central nervous system (Tian, Zhang et al. 2025), but its effects on the enteric nervous system (ENS) have not been defined. In this study, using immunofluorescence and RNA sequencing, we compared the impacts of KO supplementation on the myenteric plexus in the distal colon with a clinically used corticosteroid, dexamethasone (DEX), in a mouse model (Winnie mice) of spontaneous chronic colitis that closely mimics human IBD. Furthermore, we explored the potential synergistic effects of combined KO and DEX treatment. Four groups (n = 10 per group) of homozygous Winnie mice (Win/Win) were treated with 10% KO, 20 ng/g DEX, KO+DEX, or saline (sham) for 28 days, and heterozygous mice (Win/Wt) served as healthy controls (n = 10 per group). Myenteric neuronal density, nerve fibre density, as well as oxidative DNA damage were assessed by immunohistochemistry. Neural-related gene expressionchanges were characterised by RNA sequencing. Gastrointestinal transit was assessed radiographically. Win/Win sham group mice exhibited extensive ENS pathology, including reduced myenteric neuronal density and reduced density of total, cholinergic, noradrenergic and sensory nerve fibres (p < 0.0001), together with increased oxidative DNA damage and broad downregulation of synaptic and receptor-associated genes. Treatment with KO or DEX alone partially ameliorated these abnormalities, whereas combined KO+DEX treatment produced the most extensive restoration of neuronal structure, neurochemical coding and axonal density, as well as total fibre density to the levels comparable with healthy controls. At the gene level, DEX and KO+DEX treatments partially restored expression of synaptic and ion channel genes suppressed in sham mice, whereas KO alone produced only a minimal transcriptomic response. All Moreover, total and gastro-caecal transit times were significantly reduced following all three treatments, approaching levels observed in healthy control mice. In conclusion, KO provides partial neuroprotective and neurorestorative effects on the ENS in chronic colitis, comparable to DEX in attenuating oxidative damage and improving gastrointestinal transit, though its effect on the neural transcriptome was more limited than that of DEX; neither KO nor DEX alone significantly restored individual nerve fibre subtypes, and full structural and transcriptional recovery was achieved only with combined KO+DEX treatment. These findings highlight the potential of KO as an adjunctive agent to corticosteroid treatment for IBD.