Zolbetuximab is a monoclonal antibody targeting Claudin 18.2 that has been approved for the treatment of advanced gastric cancer in Japan. Zolbetuximab has its anticancer effects through a variety of mechanisms, including antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Previous studies have identified edema and hypoalbuminemia as adverse events associated with zolbetuximab treatment although the mechanisms underlying these effects remain unclear. In this report, we present a case of zolbetuximab-inducing protein-losing gastroenteropathy in a patient with advanced gastric cancer. This case demonstrated protein leakage from the upper gastrointestinal tract, confirmed through protein leakage scintigraphy. This finding could provide the mechanisms of zolbetuximab-induced edema and hypoalbuminemia.