Since biological molecular machines such as molecular motors, cell signal processors, DNA transcription processors and protein synthesizers are only nanometers in size and have a flexible structure, they are very prone to thermal agitation. Furthermore, the input energy level is not much different from that of average thermal energy, kBT. Molecular machines can use this thermal noise with a high efficiency of energy conversion for their functions. This is in sharp contrast to man-made machines that operate at energies much higher than thermal noise. In recent years, single molecule imaging and nano-technologies have rapidly been expanding to include a wide range of life science applications. The dynamic properties of biomolecules and the unique operations of molecular machines, which were previously hidden in averaged ensemble measurements, are now being unveiled. The aim of our research is to approach the engineering principle of adaptive biological systems by uncovering the unique operation of biological molecular machines. Here, I review our single molecule experiments designed to investigate molecular motors, enzyme reactions, protein dynamics and cell signaling, and discuss how thermal fluctuations (noise) play a positive role in the unique operation of biological molecular machines allowing for flexible and adaptive biological systems including cell and brain.