Background The incidence of inflammatory bowel diseases (IBD) has increased over the last century. Despite the unclear etiology of IBD, significant advancements have been made in recent years to understand the development of this disease. Objectives The aim of this study was to examine the diagnostic significance of several inflammatory biomarkers and their associations with clinical and endoscopic disease activity in patients with IBD. Methods This case-control study involved 68 patients, 34 with Crohn's disease (CD) and 34 with ulcerative colitis (UC), with IBD confirmed by endoscopy and histopathology, and 52 healthy subjects as a control group. A pre-designed questionnaire was completed for each subject. Stool samples were taken for fecal calprotectin (FC) measurement by enzyme-linked immunosorbent assay (ELISA), and a blood sample was obtained for complete blood and differential counts using a hematology autoanalyzer, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) by Cobas (Roche Diagnostics, Basel, Switzerland), and measurements of interleukins (IL-6, IL-17A, IL-8, and IL-1β) by ELISA. Comparisons of parameters were considered statistically significant at the P < 0.05 interval. Results The mean levels of ESR, CRP, FC, all measured ILs, neutrophil number and percentage (%), neutrophil-lymphocyte ratio (NLR), and platelet number were statistically significantly higher in patients with IBD compared to the control group. However, lymphocyte%, lymphocyte-mid-size leukocytes ratio (LMR), hemoglobin, mean corpuscular hemoglobin (MCH), hematocrit, and red cell distribution width (RDW) were significantly lower in patients with IBD compared to controls. Receiver operating characteristic (ROC) curve analyses showed that FC, IL-8, and ESR, respectively, have the highest area under the curve (AUC) and were of the highest validity to differentiate between patients with IBD and healthy subjects, followed by CRP and IL-1β. Conclusion All the studied ILs were increased in patients with IBD; their increases were not different between UC and CD patients. FC, IL-8, and ESR were of the highest validity for the diagnosis of IBD. Findings collectively highlight the validity of the measured parameters as potential biomarkers in IBD.