Introduction: Inflammatory bowel disease (IBD) is a systemic disease with immune abnormalities that can affect the entire digestive tract. A high percentage of patients with IBD are unresponsive to current pharmacological agents, hence the need exists for novel therapeutic approaches. There is compelling evidence that macrophage polarization plays a key role in the remission of IBD patients and that it could open up future treatment options for patients. Areas covered: This paper highlights the crucial role of macrophage polarization in IBD. The authors shed light on the phenotype and function of macrophages and potential drug targets for polarization regulation. Existing approaches for regulating macrophage polarization are discussed and potential solutions for safety concerns are considered. We performed a literature search on the IBD and macrophage polarization mainly published in PubMed January 2010–July 2020. Expert opinion: Evidence indicates that there are fewer M2 macrophages and a high proportion of M1 macrophages in the intestinal tissues of individuals who are non- responsive to treatment. Regulating macrophage polarization is a potential novel targeted option for IBD treatment. Improved mechanistic insights are required to uncover more precise and effective targets for skewing macrophages into a proper phenotype.