Understanding the roles of asphaltene and resin as natural surfactants existed in crude oil can enlighten contradicting reported results regarding interfacial tension (IFT) of crude oil/aqueous solution as a function of salinity and ion type. In this way, this study is aimed to investigate the effect of these natural surface active agents on IFT of with special focus on SO42− anion and Mg2+ cation. Two different synthetic oil solutions of 8 wt% of the extracted asphaltene and resin dissolved in toluene are prepared, and then IFT values are measured. After that, the obtained results are compared with the IFT of intact crude oil in contact with the same saline solutions examined in the previous stage. The obtained results showed a synergistic effect of Na2SO4 + MgCl2 solution unlike the MgSO4 + MgCl2 and CaSO4 + MgCl2 solutions on IFT reduction of resin at MgCl2 concentration of 15000 mg·kg−1. In summary, it is found that the affinity of asphaltene molecules towards the interface of oleic phase/ionic solution leads to higher IFT variation.