Context: Numerous studies have shown the high frequency and antibiotic-resistant patterns of Shigella species in different provinces of Iran. In this study, we performed a comprehensive review from 2000 to 2020 in Iran to describe the prevalence rate and antibiotic-resistant patterns of S. sonnei, S. dysenteriae, S. flexneri, and S. boydii. Evidence Acquisition: We systematically searched the biomedical databases including Scopus, Google Scholar, PubMed, SID, and Web of Science for related articles published in English or Persian. Finally, out of 70 articles, 34 studies were included in the study. Results: From 44,292 clinical specimens, 2,742 cases were introduced as positive samples for Shigella species in Iran during 2000-2020. Also, S. sonnei (n = 1484, 54.1%) was the predominant species in Iran, followed by S. flexneri (n = 1100, 40.1%), S. dysenteriae (n = 80,3%), and S. boydii (n = 78, 2.8%). These Shigella species showed maximum resistance to ampicillin (n = 1759, 64%-96%), cotrimoxazole (n = 1220, 87%-100%), nalidixic acid (n = 649, 10%-82%), trimethoprim-sulfamethoxazole (n = 459, 80%-98.5%), cefotaxime (n = 410, 53%-63%), and tetracycline (n = 386, 36%-94%). No resistances were found against imipenem, meropenem, cefoxitin, norfloxacin, levofloxacin, azithromycin, and amoxicillin. Also, 308 and 359 cases were introduced as multidrug resistance (MDR) and extended spectrum beta lactamase (ESBL) producing species, respectively. Conclusions: Evaluation of endemic shigellosis and antibiotic-resistant patterns through epidemiological studies are necessary to promote infection control strategies. These data may be useful to avoid empirical treatment, revise treatment guidelines, and decrease antimicrobial resistance of Shigella spp. in human societies.