The current study presents a novel and effective cavitation technique for the degradation of phenol using a hydrodynamic cavitation‐based packed bed reactor (HCPBR). Several operational parameters, including fluid velocity, hydrogen peroxide (H2O2) generation (18.06 μM of H2O2 in 60 min), and initial phenol concentration, have been studied using a HCPBR. The effective parameters for phenol degradation were found to be a fluid velocity of 85.15 m/s and an initial phenol concentration of 20 ppm. It was also noted that the presence of a glass marble‐bed (15.35%) in the cavitation reactor exhibits a substantial effect on the degradation of phenol compared to the absence of a glass marble‐bed (2.91%). The investigation also examined the effect of combining hydrodynamic cavitation with chemical oxidation processes, specifically H2O2, persulfate (Na2S2O8 and K2S2O8), and titanium dioxide, on the extent of phenol degradation. Persulfate was shown to have a significant effect on phenol degradation at 1 g/L. To clarify if free radical attack is the driving force behind degradation, the impact of radical scavengers such as n‐butanol has also been examined. Toxicological assessments revealed that, for lentil meristematic cells, the therapy was quite cytotoxic, but it needs to be improved to eliminate its genotoxic side effects. Overall, the experiment clearly demonstrated the effectiveness of the HCPBR for phenol degradation.