Since, oxidative stress has been suggested as one of the mechanisms underlying arsenic-induced toxicity, the present study focused on the role of antioxidant (curcumin) supplementation on behavioral, biochemical, and morphological alterations with context to mice hippocampus (CA1) following arsenic trioxide (As2O3) administration. Healthy male Swiss albino mice were divided into control and experimental groups. As2O3 (2 mg/kg bw) alone or along with curcumin (100 mg/kg bw) was administered to experimental groups by oral route for 45 days whereas the control groups received either no treatment or vehicle for curcumin. Animals were subjected to behavioral study towards the end of the experimental period (day 33–45). On day 46, the brain samples were obtained and subjected either to immersion fixation (for morphometric observations) or used afresh for biochemical test. Behavioral tests (open field, elevated plus maze, and Morris water maze) revealed enhanced anxiety levels and impairment of cognitive functions in As2O3 alone treated groups whereas a trend of recovery was evident in mice simultaneously treated with As2O3 and curcumin. Morphological observations showed noticeable reduction in stratum pyramidale thickness (CA1), along with decrease in density and size of pyramidal neurons in As2O3 alone exposed group as compared to As2O3 +Cu co-treated group. Hippocampal glutathione levels were found to be downregulated in animals receiving As2O3 as against the levels of controls and curcumin supplemented animals, thereby, suggestive of beneficial role of curcumin on As2O3 induced adverse effects.