A large number of researchers have endeavored to delineate the effects of injecting brine with a low ionic strength in oil reservoirs in the past decade. However, we still cannot conclude the overriding mechanism(s) of recovering oil from this technique. Even with a detailed review of the literature, the effect of low-salinity water flooding (LSWF) shows that a bewildering array of conflicting results have been reported. From the physicochemical point of view, understanding how brine and oil chemistry affects oil recovery helps to optimize recovery from such processes. Furthermore, the use of brine with low ionic strength coupled with nanoparticles during enhanced oil recovery (EOR), especially in the presence of monovalent ions and/or divalent cations, presents a new field of study that requires further investigations. Herein, the main objective of this study was to investigate the fluid/ rock interactions at different salinities in the presence of various surface-modified pyroxene nanoparticles. Pyroxene was surface modified using polyethylene amine (PEI), poly(ethylene oxide) (PEO), and triethoxyoctylsilane (TOS). Surface charge, wettability measurements in the presence of various ions in the irreducible water, and core flooding experiments have been conducted to understand the underlying mechanism(s). The surface charge was evaluated by zeta potential measurements, and wettability was determined by the contact angle, imbibition, and relative permeability measurements. Sandstone outcrops and three oil samples with different composition were used. The results show that adding 0.005 wt % nanoparticles to brine with low ionic strength (1000 ppm) can improve the nanofluid stability and EOR. Additionally, in the presence of LSWF combined with nanoparticles, the thickness of the double layer on the rock surface greatly expands, thus increasing the magnitude of zeta potential compared to LSWF alone. The contact angle in the presence of LSW alone and N-PEO, N-PEI, and N-TOS nanofluids was measured as 94 ± 3, 118 ± 3, 112 ± 3, and 130°± 3°, respectively, conforming wettability alteration from oil/neutral wet to stronger water-wet. Moreover, the greater repulsive force due to double-layer expansion creates a significant shift in the relative permeability curve to the right. Consequently, this results in improved oil recovery by about 15% of the oil originally in place. Based on the obtained findings, LSWF coupled with nanoparticles provides a prospect of being applied in EOR.