Abstract Background Fetomaternal outcomes are of primary concern for gastrointestinal (GI) endoscopy in pregnancy. We aimed to systematically review the safety and utility of endoscopic procedures in pregnancy. Methods A systematic literature search was performed using PubMed. All original research articles with sample size > 10 involving endoscopy in pregnancy were included for the review along with case report/series describing novel/rare techniques from 1948 to July 2021. Results After screening 12,197 references, 216 citations were found and finally 66 references were included. Esophagogastroduodenoscopy had favorable fetal outcome (>95%) based on two large retrospective studies and a review of case reports. Sclerotherapy and band ligation of varices were safe according to case series. A large nationwide cohort study established safety of endotherapy for nonvariceal bleed. Botulinum toxin and pneumatic dilation in achalasia are only supported by case reports. Percutaneous endoscopic gastrostomy can be useful to support nutrition based on case reports. A retrospective case–control and cohort study with systemic review justified flexible sigmoidoscopy if strongly indicated. Low birth weight was more common when sigmoidoscopy was done in inflammatory bowel disease based on a prospective study. Colonoscopy was considered safe in second trimester based on a case–control study whereas it can be performed otherwise only in presence of strong indication like malignancy. Capsule endoscopy is promising and can be useful in acute small bowel bleeding although risk of capsule retention is unknown. There are no reports of enteroscopy in pregnancy. Twelve retrospective studies and one prospective study showed high success rate of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) (> 90%) in all trimesters and can be performed if strongly indicated. Pregnancy was an independent risk factor for post-ERCP pancreatitis in a large nationwide case–control study. Radiation-free ERCP with wire-guided bile observation, stent-guided or precut sphincterotomy, endoscopic ultrasound (EUS) guidance, and spyscopy have been described. Safety of EUS is limited to case series and can be used in intermediate probability of choledocholithiasis to guide ERCP and endoscopic cystogastrostomy. Conclusion This review concludes that GI endoscopy during pregnancy can be done effectively if strongly indicated with good fetomaternal outcomes. Precautions are advocated during procedures where radiation exposure is expected.