The present work investigated the degradation of cefixime (C16H15N5O7S2) using a synergy of sonochemical effects with oxidant radical promoters such as hydrogen peroxide and sodium persulfate. Complex hydrocarbon chain of cefixime degraded using different approaches viz, ultrasound + H2O2 (USH), ultrasound + sodium persulfate (USSP), and combined approach ultrasound + H2O2 + persulfate (USHSP). The optimum oxidant dosing was found to be 1:40, 1:50, and 1:20, and the percentage degradation was 74.2, 65.9, and 74.9 for USH, USSP, and USHSP, respectively. The degradation results are also supported by kinetic rate analysis. The maximum kinetic rate constant was observed for USHSP compared to USP and USSP. The time required for degradation using USHSP was half compared to other combinations. The pseudo-first-order kinetic rate constant for USP, USSP, and USHSP was 4.32, 5.32, and 8.40 min-1. The effect of USSP was marginally higher compared to USH and USHSP but the oxidant produced was useful for complete mineralization of cefixime. Total organic carbon removal was 53.2, 83.2, and 79.1% for USP, USSP and USHSP, respectively. Antimicrobial analysis of the treated sample confirmed the degradation results and maximum survival of E. Coli. the strain was found in USH, USSP, and USHSP.