Introduction: The overuse and improper disposal of antibiotics may add to the continuous rise of antimicrobial resistance (AMR). In this work, we demonstrate a sequential effect of two novel catalytic systems consisting of MIL-100(Fe) MOF (Metal Organic Framework) and MnO2 nanosheets to degrade amoxicillin antibiotic through the destruction of β lactam group. Method: The catalysts exhibit large surface area, excellent porosity, excellent catalytic activity, and insolubility and can be easily separable from the reaction mixture. Results: The sequential use of MIL-100(Fe) MOF and MnO2 nanosheets could showcase 92% degradation of amoxicillin within 1.5 hours under ambient conditions without any significant residual bi-product as confirmed by LCMS studies. Conclusion: Impressively, the antimicrobial susceptibility of degraded residue is lessened by 33% as compared to pure amoxicillin. result: we have successfully developed a two-part method to completely degrade amoxicillin, a commonly used antibiotic. This method utilizes catalysts, MnO2 nanosheets and Fe-MIL 100 MOF, applied sequentially. both catalysts are reusable, non-toxic, and easily separated from the reaction. In just 1.5 hours at normal conditions, this approach achieved 91