Esophageal stricture can be an adverse event following endoscopic submucosal dissection (ESD). Although particle-shaped materials could prevent post-ESD esophageal strictures, no applicator can efficiently deliver them to the ESD wound site. In this study, we developed an applicator to endoscopically deliver powders by combining polytetrafluoroethylene (PTFE) tubes and five types of catheter-tip nozzles with different structures fabricated using a 3D printer. The applicator with a T3S4 nozzle, with three and four holes on the tip and side, respectively, achieved lateral powder delivery from the endoscope catheter tip. The adhesion percentage to the ESD wound site, estimated using the esophagus mimicking model setup with tubes and wetted laboratory wipes, increased from 25 % (without the nozzle) to 55 % (with the T3S4 nozzle). In the computational fluid dynamics (CFD) simulation without a nozzle, the powder particles went straight, and hardly adhered to the ESD wound site. By contrast, the CFD simulation with the optimized T3S4 nozzle predicted that the adhesion percentage would increase by up to 55 %. Optimization of the axial position of the catheter affected the powder delivery efficiency, while optimizing the radial position and angle affected the homogeneity of powder delivery. An in vivo porcine ESD model using the developed applicator confirmed efficient and homogeneous powder delivery to the ESD wound site. These results suggest that the powder applicator development and CFD simulations are effective in treatments using endoscopic powder delivery.