The improvement of the sono-photo-Fenton process at nearby neutral pH (~ 6.2) and high iron concentration (5 mg L-1) by the addition of the juice of Passiflora edulis f. flavicarpa Degener (yellow passion fruit) on the degradation of imipenem in water is reported for the first time. Considering that the combination of sonochemistry with photo-Fenton takes advantage of the in situ sonogeneration of H2O2, the effects of frequency and acoustic power for the H2O2 accumulation were established initially. The sonication at 578 kHz and 23.8 W favored the H2O2 generation. Using such frequency and power, the antibiotic was synergistically degraded by the sono-photo-Fenton system in distilled water, leading to ~ 90% removal at 120 min of treatment. An atomic charge analysis showed that thioether, β-lactam ring, and carboxylic acid moieties on the imipenem structure were very prone to interactions with the HO• generated in the sono-photo-Fenton process. Indeed, the primary transformation products (TPs) came from the oxidation of the thioether, the opening of the β-lactam ring, and decarboxylations. Such TPs had a lower probability than imipenem to be active against bacteria. Besides, the addition of small amounts (2.5-10 µL) of the yellow passion fruit juice to the sono-photo-Fenton system significantly improved the pharmaceutical elimination. However, a juice excess (e.g., 100 µL) caused a detrimental effect due to competing effects by radicals. The juice of the yellow passion fruit induced analogous effects to citric acid (a commercial complexing agent) on the sono-photo-Fenton process. Indeed, the degradation of imipenem in simulated hospital wastewater by sono-photo-Fenton was improved by the yellow passion fruit juice (~ 38% at 60 min), and it was similar to that with citric acid (~ 39% of removal at 60 min). Thus, the commercial reagent can be replaced by a natural and low-cost complexing agent (e.g., yellow passion fruit juice or fruit wastes containing citric acid), as an enhancer of the sono-photo-Fenton process carried out at near-neutral pH and high iron concentration for degrading imipenem in water.