Abstract: Objective To investigate the effect of calcitriol supplementation on oxidative stress and insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). Methods A total of 91 patients with NAFLD were screened and 68 were included in this study. According to the level of serum 25 (OH) D₃, 68 patients were divided into three groups: vitamin D deficiency group, vitamin D insufficiency group and vitamin D normal group. NAFLD patients in vitamin D deficiency group and vitamin D insufficiency group were given 0.25 μ g /d of calcitriol and were followed up for 12 weeks. Finally, 57 patients (there were 14 cases in vitamin D deficiency group, 19 cases in vitamin D insufficiency group and 24 cases in vitamin D normal group) completed the study and were included in the analysis. The changes of the various parameters before and after the supplementation of calcitriol were compared. Results The levels of high-sensitivity C-reactive protein (hs-CRP) and methylenedioxyamphetamine (MDA) of NAFLD patients in the vitamin D deficiency group and vitamin D insufficiency group were higher than those in the vitamin D normal group, while the level of superoxide dismutase (SOD) was lower than that in the vitamin D normal group (P<0.05). After correction of confounding factors, the difference was still statistically significant (P<0.05). In addition, the homeostasis model assessment of insulin resistance (HOMA-IR) in the vitamin D deficiency group and vitamin D insufficiency group was also significantly higher than that in the vitamin D normal group (P<0.05). After intervention with calcitriol for 12 weeks, the level of serum 25 (OH) D₃ in the vitamin D deficiency and vitamin D insufficiency NAFLD patients increased significantly (P<0.01), the levels of hs-CRP and MDA decreased significantly (P<0.05), the level of SOD increased significantly (P<0.01), and fatty liver index (FLI) decreased significantly (P<0.05), but HOMA-IR did not show significant changes (P>0.05). Conclusions Calcitriol suplementation can improve the oxidative stress response of NAFLD patients with vitamin D deficiency and insufficiency, but has no significant effect on insulin resistance.