Traditional hard tissue grippers are limited in handling delicate soft tissues during surgery, particularly due to the high stress points that are generated on the soft tissue during gripping. In this study, customizable soft pneumatic chamber–gripper devices were designed to provide compliant gripping, so as to replace conventional tissue grippers such as the laparoscopic grasper or forceps in delicate tissue manipulation. The soft chamber–gripper device involves very simple design and control to generate actuation. It is fabricated from an elastomeric material using a modified soft lithography technique. The device consists of a gripper component that can be made up of one or more gripper arms with a pneumatic channel in each arm, and a chamber filled with air. The pneumatic channels are positioned close to the outer wall of the gripper arms and are connected to the chamber. Upon compression of the chamber, the pneumatic channels will inflate towards the outer walls, which thus bends the gripper arms and results in a closed gripping posture. This soft chamber–gripper device can be used to pick up objects of size up to 2 mm with a compressive force that is more than three times smaller than the grip force generated by traditional forceps. This will be useful in preventing tissue trauma during surgical manipulation, especially in nerve anastomosis.