The iron-based metal−organic framework (NH 2 -MIL-101(Fe)) nanoparticles exhibited excellent conductivity, exceptional catalytic effect, sturdy stability flexible structure, etc. Consequently, it has been exploited in various applications. Herein, NH 2 -MIL-101(Fe) nanoparticles were successfully synthesized via the hydrothermal method and were grown in situ onto the pencil core electrode (PCE) for simultaneous determination of caffeic acid (CA) and acetaminophen (AP). The PCE decorated by NH 2 -MIL-101(Fe) as electrode substrate, combined with the dual effects of the excellent electrocatalytic activity of NH 2 -MIL-101(Fe) and the commendable electrical conductivity of PCE, the constructed sensor exhibits superior electrochemical sensing activity. The electrochemical behavior of CA and AP at the electrodes were investigated mainly by differential pulse voltammetry (DPV) and cyclic voltammetry (CV), exhibiting broad linear responses from 0.1 to 500 μM, and 0.08 to 800 μM for simultaneous detection of CA and AP, with detection limits of 29 nM and 24 nM, respectively. Moreover, the results of CA and AP in drug and human urine using this sensor were satisfactory, which proved that the sensor is feasible to simultaneously detect CA and AP.