Bisphenols are important industrial materials for example for the production of plastics, but are also well known for their adverse health effects, in particular bisphenol A (BPA) is an endocrine disruptor. The widespread use of plastics has raised concerns. Therefore, the removal of bisphenols from wastewater has sparked the interest of the scientific community. This work introduces a novel hybrid technique of micro-nano bubbles assisted laccase (MNB-Lac) to degrade bisphenols in water. The feasibility of MNB-Lac using BPA as a model contaminant was evaluated by comparing with MNB, Lac, ultrasound (UL), UL-Lac, and UL-MNB-Lac. Comprehensive investigations were carried out to understand the specific influences of key process parameters including the initial pollutant concentration, temperature, air intake, pH, outlet pipe length, and Lac concentration on BPA degradation. The alkaline environment and extended length of outlet pipe could improve the degradation efficiency further. MNB-Lac exhibited 2.3–6.2 folds higher BPA degradation and less time than the other above process under the optimal parameters. The mechanism of MNB-Lac revealed that the generation of hydroxyl radical, high O₂ solubility, and high mass transfer efficiency induced by MNB play important roles on enhancing the degradation catalyzed by Lac. MNB-Lac was successfully used for treating bisphenol B, bisphenol C, and the mixture of three bisphenols with high removal efficiency. Subsequently, these degradation products were analyzed by GC–MS. MNB-Lac potentially represents an innovative technology with considerable advantages in contaminant cleanup and time efficiency for treating phenolic contaminated water. Furthermore, the findings provide new insights into the enhancement of the performance of an oxidizing enzyme by introducing MNB technology.