Abstract: Although, positive role of special bacteria in induction of Inflammatory Bowel Disease (IBD) including Ulcerative Colitis (UC) and Crohn’s Disease (CD) have been demonstrated in several studies but the consensus on etiology of IBD and beneficial effect of antibiotics has not been reached yet. And, also, no well-designed clinical trials in this regard have been done yet. This review focuses on various clinical trials which have been done in according to beneficial use of antibiotics in UC and CD from 1978 to date. For this purpose, all electronic databases such as PubMed, Scopus, Google Scholar and Cochrane library were searched. The results of clinical trials suggested that metronidazole, ciprofloxacin or the combinations of these antibiotics are effective in CD. However, ciprofloxacin is the first choice, because it has good coverage on gram negative and anaerobic bacterium which plays an important role in CD. However, there is a controversy on the use of antibiotics in UC and the efficacy of them in long-term treatment of UC is still in doubt. Various antibiotics such as anti-tuberculosis, macrolides (clarithromycin), fluoroquinolones, 5-nitroimidazoles, rifaximin, rifamycin derivatives (rifampin), aminoglycosides (tobramycin), rifabutin, clofazimine, tetracyclines (tetracycline and doxycycline) and vancomycin have been under attention of researchers in the recent years. Furthermore, other antibiotics with lower cost and adverse effects, effectiveness and availability are the third generation of cephalosporins and gentamicin and also penicillin or clindamycin that should be evaluated in future studies.