Colonoscopy (CLN) is a common procedure for colon cancer screening and diagnosing various conditions. Acute cholecystitis (AC), though rare, has been reported as a complication. We present a 66-year-old female on semaglutide for obesity who developed AC within 72 hours post-CLN. Considering the increasing use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and their impact on gallbladder motility, these medications may contribute to this complication. Future research is crucial to investigate whether a washout period for GLP-1 agonists before CLN is needed to reduce the risk of AC, if such a risk exists.