Purpose Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare disease with unknown risk factors. The role of oxidative stress and nutritional factors is imprecise in NMOSD development. Therefore, this paper aims to evaluate the effects of dietary total antioxidant capacity (TAC) on the odds of NMOSD. Design/methodology/approach Dietary TAC was determined in 70 definite NMOSD cases and 164 healthy controls in term of Ferric Reducing Antioxidant Power (FRAP) method. A validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment. Three multivariate regression models were applied to analyze the odds of NMOSD across the TAC quartiles. Findings A significant inverse association was found between dietary TAC and odds of being assigned to the NMOSD group in all three regression models. In the fully adjusted model ORs (95% CI) in the second, third and fourth quartiles of TAC vs the first quartile were as follows: 0.11 (0.04-0.29), 0.05 (0.01-0.16) and 0.01 (0.00-0.05), respectively. Odds of NMOSD also indicated a significant decreasing trend across the quartiles of dietary TAC (p-trend: <0.01). Total energy (p < 0.01) as well as consumption of vegetables (p < 0.01), whole grains (p < 0.01), tea and coffee (p < 0.01), legumes (p < 0.01) and poultry (p < 0.01) significantly increased through the TAC quartiles. Originality/value In the present study, a new hypothesis was proposed concerning the influence of dietary TAC on the odds of NMOSD. A diet rich in foods with high TAC can be effective in the modification of the NMOSD odds.