Hyperkalemia in patients with renal insufficiency could be life-threatening. One method for treating hyperkalemia is with sodium polystyrene sulfonate (kayexalate), a cation-exchange resin. While some minor gastrointestinal disturbances, such as constipation, anorexia, and nausea, are known side effects, there have also been reports of serious gastrointestinal complications. Here, we present a Taiwanese female patient with acute diarrhea, acute kidney injury, and hyperkalemia who developed colon necrosis with bloody stool as a result of oral kayexalate treatment. This case later complicated with colon polyp formation and stricture. Careful use of the drug could help avoid unnecessary complications.