Low saline water flooding (LSWF) had proved to be an efficient method for enhanced oil recovery in clay-bearing hydrocarbon reservoirs, but the interaction mechanisms among in-situ rocks – fluids and injection fluids within the reservoir – are not yet known properly. Understanding the molecular level interaction among these components is critical for designing and field scale implementation of LSWF in clay-bearing crystalline reservoir rocks, which is very limited in the existing literature. A weathered amphibolite rock and one dead crude oil from the Bakrol field (Cambay basin, India) have been used in this study. The presence of clay minerals in the weathered amphibolite rock was observed using a polarising microscope and characterised by the X-ray diffraction (XRD) and Fourier transform infrared (FTIR) techniques. The crude oil and its fractionated SARA components have been extensively studied by spectroscopic techniques for their characterisation. The interaction study among the rock powder, hydrocarbon crude oil and saline water has been performed in the present work for gaining better insight for designing the injection fluid for LSWF. The weathered amphibolite rock powder was mixed with the dead crude oil and kept for 30 days in room temperature (T) and pressure (P) for proper interaction. The XRD, FTIR and cation exchange capacity results clearly demonstrated the incorporation of crude oil components in the interlayer surfaces of clay minerals. The oil removal efficiency, from the oil-treated rock powder of three saline water samples having NaCl concentration of 3000, 5000 and 8000 ppm, was investigated using the UV–Vis and fluorescence spectroscopies. The low saline NaCl water is capable of removing the maximum amount of polar components from the oil-treated rock powder. These molecular level insights are valuable for designing effective injection fluid for enhancing the oil recovery from the clay-rich crystalline reservoir rock.