One of the nanomaterial-based antimicrobials, CuS, has emerged as a potential active therapeutic agent to combat biofilm infections, showing superior antibacterial activity with both photothermal and photodynamic effects under NIR illumination. To investigate the influence of transition metals on the antibacterial activity of CuxS, the antibacterial properties of shape- and phase- controlled copper-based multinary sulfide (M: CuxS (M: Mn, Zn and Ni)) nanostructures prepared by hot injection method were investigated against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli under NIR light irradiation. It has been shown that CuxS-based nanomaterials suppress bacterial growth under NIR light irradiation and that, in addition to their antibacterial activity, they also exhibit a remarkable ability to form biofilms. The antibiofilm efficacy of the M:CuxS (M: Mn, Zn and Ni) nanocomposites was significantly higher than that of bare CuS, resulting in biofilm inhibition with rates of 52.53 %, 62.24 % and 74.48 % on E. coli for Mn:CuxS, Zn:CuxS and Ni:CuxS, respectively. In addition, the biofilm of S. aureus was more affected by treatment with M:CuxS (M: Mn, Zn and Ni) nanocomposites, with biofilm activity of 64.15 %, 68.42 % and 87.35 % for Mn:CuxS, Zn:CuxS and Ni:CuxS, respectively. Ni:CuxS showed the highest antibacterial activity, which is attributed to smaller crystal and particle size and energy band gap, resulting in a larger number of nanoparticles per unit volume, a larger surface area and a stronger tendency to electrostatically bind to bacterial cell membranes, a faster ability to penetrate channels and stronger absorption in the NIR range. This work points the way for a broad application of CuS-based biocompatible synergistic antibacterial nanocomposites and can also serve as a guide for antibacterial/antibiofilm approaches as an alternative to conventional antibiotic treatments.