Objective To establish the contact deformation model of biological tissues contacting with endoscopic instruments, and to make mechanical analysis on contact stress and strain. Methods Based on Kelvin-Voigt model and Hertz contact theory, the contact deformation model of instruments (with both wedge-shaped teeth and cylinder-shaped teeth) contacting with biological tissues was established, and the variation of contact stress and strain changing with time in different endoscopic instruments were obtained through finite element analysis method and bio-impedance measurement. Results Endoscopic instruments with different structures of the teeth could cause different strain and stress on tissues during laparoscopic grasping. The stress of the instrument with wedge-shaped teeth on tissues was largest, while that with cylinder-shaped teeth was smallest, and that of instrument with hybrid structure of wedge-shaped and cylinder-shaped teeth was in between. Conclusions The hybrid structure of wedge-shaped and cylinder-shaped teeth can effectively reduce the peak pressure during laparoscopic grasping, thus prevent less tissue damage caused by wedge-shaped teeth, and enhance the grasping ability with cylinder-shaped teeth. This study provides an important reference for the safety use and better design of laparoscopic instruments in clinic.