Abstract: As scientific quests and engineering applications delve down to a nanometer scale, there is a strong need to fabricate nanostructures with good regularity and controllability of their pattern, size, and shape. In many applications, furthermore, the nanostructures are not useful unless they cover a relatively large area and the manufacturing cost is within an acceptable range. The first part of this dissertation describes an effective nanofabrication method to create a uniform nano-periodic (∼200 nm in pitch) silicon structures (post and grate) of varying shapes and heights (up to microns) over a large sample area (2x2 cm2), enabled by coupling interference lithography with deep reactive ion etching (DRIE) in one process flow. Interference lithography is a relatively simple way to make submicron-scale patterns over a large area with superior control of pattern regularity. Sidewall profiles of the nanostructures are controlled by regulating etching parameters in Bosch DRIE. Size and tip sharpness are further elaborated with thermal oxidation and subsequent removal of the oxide. The well-defined nanostructures over a large cover area with controllable sidewall profiles and tip shapes open new application possibilities in the areas beyond nanoelectronics. As the first engineering application, a large slip effect and the corresponding friction reduction of liquid flow are demonstrated by using a nanoengineered superhydrophobic surface. While many recent studies have confirmed the existence of liquid slip over certain solid surfaces, there has not been a deliberate effort to design and fabricate a surface that would maximize the slip under practical conditions. The nanoengineered superhydrophobic surface minimizes the liquid-solid contact area so that the liquid flows predominantly over a layer of air generating dramatic slip effect and friction reduction, even under pressurized flow conditions. As the second application, cell behaviors on various nanotopographies are investigated on well-regulated nanostructure systems of post and grate patterns of 230 nm periodicity and varying heights. Cells live in nanofeatured environment in vivo, where they interact with various three-dimensional (3D) nanotopographies. Unique cell proliferation, morphology, and adhesion were observed according to the varying 3D nanotopographies, suggesting that the results may lead to many potential applications in bioengineering in general, tissue engineering in particular.