This work describes the degradation of synthetic water containing an elevated NAP concentration using the ultrasound and commercial Laccase enzyme (LT-100) by optimizing the system's parameters, such as ultrasound power, % duty cycle, enzyme concentration, and thermal environment. The established optimum condition obtained at a temperature of 40 degrees C, enzyme concentration 0.15% (w/v), ultrasound power 50 W, and 50% duty cycle of 10 min resulted in extreme NAP degradation of 96% in a time of 150 min. A noticeable improvement (67%) in the degradation of NAP was observed with enzyme and ultrasound than in the ultrasound only. An ultrasound-assisted enzymatic reaction showed a significant synergy effect under US irradiation, as evidenced by synergetic index values ranging from 0.873 to 1.841 for NAP. Radical scavenging experiments and LC/MS analysis revealed that hydroxylation, demethylation, and decarboxylation are the main chemical mechanisms involved in the degradation of NAP. The kinetic study showed that the degradation of NAP follows Michaelis Menten's kinetics having Vmax and Km as 3.3 & mu;M/min and 18.3 & mu;M, respectively. Low Km finding indicates there is much more enzyme compatibility towards the substrate. Furthermore, a toxicity study conducted on Naproxen revealed that the solutions obtained after the process exhibited approximately 80-85% less toxicity compared to the initial naproxen solutions.