Crohn’s disease is a chronic inflammation of the gastrointestinal tract without any signs of infection. It is a prolonged disorder characterized by recurring attacks. Disease may occur in any segment of the colon, ranging from the oral cavity to the rectum. Anti-Saccharomyces cerevisiae (ASCA) are used to subtype patients with CD from ulcerative colitis (UC). IL-37 is an identified member of the IL-1 family that exhibits anti-inflammatory properties. Several genetic variations in cytokine genes have been linked to an elevated risk of developing autoimmune disorders. However, an association between genetic variations in the IL-37 gene and a decrease in serum IL-37 levels in CD has not been investigated. The aim was to find out the association between IL-37 genetic variants, IL-37 plasma levels, and various clinical phases of Crohn’s disease. Serum concentrations of IL-37 and ASCA were evaluated using ELISA, and genetic variants were genotyped by conventional polymerase chain reaction (PCR) and the sanger sequence technique. It was found that the G>A genotype of (rs3801147) occurs significantly more frequently in patients with active CD. Since the allele G is considered a common allele in patients, it may have a good etiological role for disease. While the allele A is considered a common allele in control, it recorded a higher protective factor rate (0.06). In addition, the G allele of the rs3801147 SNP wasn’t associated with low circulating concentrations of IL-37. Furthermore, low circulating concentrations of IL-37 may have a negative correlation between the levels of IL-37 and the severity of CD.