The increasing demand for wastewater treatment has become a notable trend for addressing global water scarcity. However, composite fouling is a significant challenge for wastewater distribution engineering systems. This study provides an approach using nanobubbles (NBs) to control composite fouling. The antifouling capacities of three types of NBs (oxygen, nitrogen, and helium), six oxygen concentrations, and two application procedures (prevention and removal) are investigated. The results show that NBs effectively mitigate composite fouling—including biofouling, inorganic scaling, and particulate fouling—in comparison with the no-NBs group. More specifically, hydroxyl radicals generated by the self-collapse of NBs oxidize organics and kill microorganisms in wastewater. The negatively charged surfaces of the NBs transform the crystalline form of CaCO3 from calcite to looser aragonite, which reduces the likelihood of ion precipitation. Furthermore, the NBs gas-liquid interfaces act as gas "bridges" between colloidal particles, enhancing the removal of particles from wastewater. While oxygen NBs have greater anti-fouling capacity than nitrogen and helium NBs, oxygen NBs at low concentrations (∼5%) increase total fouling. Lastly, although the NBs inhibit the growth of fouling, they do not significantly remove the already adhered fouling in no-NBs treated groups. This study anticipates that the application of NBs will address the significant fouling issue for various wastewater distribution engineering systems in order to meet the global challenge of sustainable water supplies.