This study investigated the capabilities of In-MOFs for detecting l-histidine concentrations through the controlled degradation of frameworks. The In-MOF was synthesized using a microwave-assisted method and characterized using a variety of analytical techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), BET surface area technique, and ATR-FTIR spectroscopy. The l-histidine concentrations were quantified using both UV-Vis spectroscopy and electrochemical impedance spectroscopy (EIS). In our research, we found that In-MOFs are promising sensing materials for L-histidine detection, particularly in relation to MOF degradation. The results of this study advance the application of In-MOFs in advanced biosensing technologies.