The near-infrared (NIR) light-absorbing AgBiS2 nanoparticles can be excited by single-wavelength light, which is the primary characteristic of a photo responsive platform. Chemical synthesis of nanomaterials inevitably requires long-chain organic surfactants or polymers to stabilize them in the nano regime. These stabilizing molecules barricade the interaction of nanomaterials with biological cells. We have produced stabilizer-free (sf-AgBiS2) and polymer-coated (PEG-AgBiS2) nanoparticles; and assessed their NIR mediated anticancer and antibacterial activity to evaluate the effect of stabilizers. sf-AgBiS2 showed better antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) and displayed excellent cytotoxicity against HeLa cells and live 3-D tumour spheroids compared to PEG-AgBiS2 both in presence and absence of NIR radiation. The photothermal therapy (PTT) results illustrated the tumour ablation ability of sf-AgBiS2, which converted light into heat effectively up to 53.3 °C under NIR irradiation. This work demonstrates the importance of synthesizing stabilizer-free nanoparticles to produce safe and highly active PTT agents. © 2023 Wiley-VCH GmbH.