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This study intends to redesign the user interface of mobile devices to ease the heavy workload on the thumb as well as to better fit our hand with the devices when grasping. Based on the motion characteristics of thumb and index finger and the one-handed operated interface requirements, a new design idea was emerged. The design principles were taken into consideration for the new interface design in order to increasing comfort and reducing muscle workload of the thumb. The method of this study is divided into two stages: new device innovation and evaluation. After experimental analysis, this study suggests: 1. Designing the contoured grasping region based on user anthropometric data for the mobile devices will provide a more comfortable grasp. 2. It is recommended that the center of keypad be located at near the thumb tip for both minimizing the joint angle changes of operating digits and enhancing the accessibility of the thumb. 3. The effort of adding index finger keys for reducing thumb fatigue level is not seem to be obvious. The results can contribute to design of one-handed mobile device.