Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing conditions resulting from immune system activity in a genetically predisposed individual. IBD is based on progressive damage to the inflamed gut tissue. As its pathogenesis remains unknown, recent accumulating data have demonstrated that IBD are complex and multi-factorial disorders correlated with host luminal factors which lead to imbalance between pro- and antiinflammatory signaling. The growing understanding of the molecular mechanisms responsible for IBD has suggested a wide range of potential therapeutic targets to treat this condition. Some patients do not have satisfactory response to current therapeutic medications such as anti-tumor necrosis factor (TNF) agents, or their response decreases over time. As a result, IBD therapeutics have been changed recently, with several new agents being evaluated. Identification of various inflammatory cascades have led to form the idea to have novel medications developed. Medications targeting Janus kinases (JAK), leukocyte trafficking Interleukin (IL) 12/23, and Sphingosine 1 phosphate (S1P) are among these newly developed medications and highlight the role of microbial-host interaction in inflammation as a safe promising strategy. This systematic review aims to summarize different molecular targeting therapeutics, the most potent candidates for IBD treatment in recent studies.