In complex environmental substance monitoring, the simultaneous detection of single and multiple substances with high sensitivity has been a research focus in the field of electrochemical sensors. Rational selection of appropriate dopants to optimize the electrode material is crucial in this regard. In this work, we employed a multi-doping strategy to effectively enhance the electrocatalytic performance of multi-walled carbon nanotubes (MWCNTs). By doping Ni/NiCx onto MWCNTs, we successfully constructed a heterojunction material (Ni/NiCx-N-MWCNTs). The successful doping of Ni/NiCx allows for the synergistic effects of multiple elements. Ni/NiCx serves as a conductive bridge, forming a three-dimensional network of nanotubes, which effectively reduces the aggregation of carbon nanotubes, exposes more active sites, and enhances electrocatalytic activity. The electrochemical sensor based on Ni/NiCx-N-MWCNTs demonstrated high sensitivity, selectivity, and simultaneous electrochemical detection for acetaminophen (1–150 μM, limit of detection (LOD)=0.56 μM) and dopamine (1–80.0 μM, LOD=0.19 μM). Its excellent reproducibility (relative standard deviation (RSD)=2.01 %) and interference resistance provide Ni/NiCx-N-MWCNTs with significant advantages over other electrode materials, indicating a promising application potential.