In modern life, technologies enabling detection of biological molecules at a low threshold, for health and ecological concerns, are in high demand. Directly interrogating the molecules is a promising direction to clarify the noisy response of conventional assays arising from simultaneous different reactions. Besides sophisticated biophysical instrument such as the atomic force microscope, this paper proposes silicon nanotweezers (SNT) as a new microsystem for molecular manipulation. SNT can trap molecules and sense their biomechanical and bioelectrical response in minute operations. In this review SNT characteristics are overviewed; their operation modes are illustrated by molecule and cell trapping, manipulation and characterization in air and in solution. As they are tiny and can be mass produced by highly parallel microsystem technology, SNT can be seen as a potential molecular and cellular probe for routine analysis and bio detection.