The 25-hydroxyvitamin D3 (25OHD3) deficiency in Crohn's disease (CD) is associated with the immune system dysfunction and redox status alteration. These two events affect intestinal mucosal function through macrophages cells infiltration and to lead a pro-inflammatory cytokines storm and ROS (reactive oxygen species) overproduction. The objective of this study was to investigate the immunomodulatory and antioxidant effects of vitaminD3 supplementation (DS3) in clinical active phase. A cohort of 262CD patients and vitaminD deficient (<50nmol/L or <20ng/mL) was randomized into 2groups according to the DS3 doses at 200,000IU/month (D200 group) versus 6,000IU/day (D6 group). Serum 25OHD3 levels were assessed before and after 6 and 12months of DS3. The clinical active phase was characterized by the CDAI score (Crohn's Disease Activity Index) and the fecal calprotectin assay. The 25OHD3 profile was analyzed by LC-MS/MS. The pro-inflammatory cytokines (TNFα, IL-6, IL-12, IL-17, IL-23) were assessed by ELISA tests. The serum trace elements (Se, Mn, Cu, Zn) was determined by mass spectrometry. The antioxidant status (TAS, SOD, GPx, GSH) was evaluated by Randox kits. The results showed that the serum 25OHD3 concentrations became normal (>75nmol/L or >30ng/mL) in the 2groups. Our data showed that vitaminD supplementation allowed the clinical remission phase. The DS3 decreased serum levels of CRPus, TNFα, IL-17 and IL-23. The DS3 modulates the trace elements ratio and increased the SOD and GPx activities. The DS3 corrects the denutrition state. The vitaminD supplementation benefits are more significant in D6 group (continuous 6,000IU/day) than in D200 group (intermittent 200,000IU/month). Our study suggests that the serum 25OHD3 profile can be considered a reliable biomarker in the bioclinic CD evolution to prevent the active phase, to extend the remission phase and to avoid the surgical bowel resection.