Clostridium species are ubiquitous and associated with various diseases in animals and humans. However, there is little knowledge about the prevalence of their resistance to antibiotics in Iran. Therefore, the aim of this study was to determine the prevalence of antibiotic-resistant Clostridium species in Iran through a meta-analysis of eligible studies published up until December 2018. Fourteen articles on the drug resistance of Clostridium species in Iran were included in the current study following a search in PubMed, Scopus and Google Scholar databases using relevant keywords and screening based on inclusion and exclusion criteria. Antibiotic resistance rates of C. difficile to ampicillin (42.8%), ciprofloxacin (69.5%), clindamycin (84.3%), erythromycin (61.5%), gentamicin (93.5%), nalidixic acid (92.9%), tetracycline (32.5%), imipenem (39.6%), levofloxacin (93.4%), ertapenem (58.7%), piperacillin/tazobactam (56.5%), kanamycin (100%), colistin (100%), ceftazidime (76%), amikacin (76.5%), moxifloxacin (67.9%) and cefotaxime (95%) were high. In addition, resistance of C. perfringens to ampicillin (25.8%), erythromycin (32.9%), gentamicin (45.4%), nalidixic acid (52.5%), tetracycline (19.5%), penicillin (21.8%), trimethoprim-sulfamethoxazole (32.1%), amoxicillin (19.3%), imipenem (38%), cloxacillin (100%), oxacillin (45.6%), bacitracin (89.1%) and colistin (40%) was high. Metronidazole and vancomycin, as the first-line therapies, fidaxomicin, tetracyclines (except tetracycline), rifampicin and chloramphenicol can still be used for the treatment of C. difficile infections. However, the present results do not recommend the use of penicillin, bacitracin and tetracycline for the treatment of C. perfringens infections in humans and domestic animals in Iran.