Water and atmospheric pollution is a major issue affecting environment and health. Semiconductor-based photocatalysis is a well-known and efficient process for achieving water and air depollution, with very limited rejects in the environment. Zinc oxide (ZnO), as a wide-bandgap metallic oxide, is an excellent photocatalyst, able to mineralize a large scale of organic pollutants in water, under UV irradiation, that can be enlarged to visible range by doping nontoxic elements such as Ag and Fe. With high surface/volume ratio, the ZnO nanostructures have been shown to be prominent photocatalyst candidates with enhanced photocatalytic efficiency owing to the facts that they are low-cost, non-toxic, and can be produced with easy and controllable synthesis. Thus, ZnO nanostructures-based photocatalysis can be considered as an eco-friendly and sustainable process. This work presents the photocatalytic activity of ZnO nanostructures (NSs) grown on different substrates. The photocatalysis has been carried out both under classic mode and micro-fluidic mode. All tests shown the notable photocatalytic efficiency of ZnO NSs with remarkable results obtained from ZnO-NSs-integrated microfluidic reactor, which exhibited an important enhancement of photocatalytic activity by reducing drastically the photodegradation time. UV-visible spectrometry and high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) are simultaneously used to follow real-time information giving both the photodegradation efficiency and the degradation mechanism of the organic dye methylene blue. By scaling-up an innovative and low-cost hydrothermal direct growth synthesis, a few square meters paved with tiling and bitumen road were easily produced in order to evaluate their photocatalytic activity at large scale under solar lamp in a climatic chamber (Sense-City, 400m2, 3200 m3) to reflect real atmospheric air purification situations. Observations provide insights into their ability to simultaneously remove various pollutants from a real car exhaust (O3, COX, NOX, VOCs) and their durability.