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Objective This study was performed to investigate whether a definite correlation exists between alteration of blood biochemical parameters and immunosuppressive therapies in patients with inflammatory bowel disease (IBD). Methods A comprehensive search of PubMed, EMBASE, MEDLINE, and the Cochrane Library was conducted. Data on alterations in white blood cells, platelets, hemoglobin, serum creatinine, and liver enzymes in patients with IBD treated with immunomodulators were extracted. Results Data from 1141 patients were included. The relative risk (RR) of leukopenia was significantly higher in the immunosuppressive therapies group than in the placebo group (RR, 12.91; 95% confidence interval [CI], 5.28–31.57). A statistically significant risk of leukocytosis during immunosuppressive therapies was observed (RR, 1.53; 95% CI, 1.05–2.23). Patients taking immunomodulators had increased risks of serum creatinine elevation (RR, 10.68; 95% CI, 2.07–55.12) and serum aminotransferase elevation (RR, 3.18; 95% CI, 1.24–8.17). Conclusion Immunosuppressive therapies might have an impact on variations in blood biochemical parameters in patients with IBD. Although the conclusion regarding leukopenia was reliable in this study, some confounding factors might reduce the reliability of the conclusions about leukocytosis, creatinine elevation, and aminotransferase elevation. Close monitoring is recommended during immunosuppressive therapies for IBD.