Water-in-crude oil emulsions cause corrosion in upstream and catalyst deactivation in downstream oil processing. It is essential to demulsify and remove aqueous impurities from oil in production facilities. In this study carboxymethyl cellulose (Walocel), cellulose acetate, and two methyl cellulose with different methyl and 2-hydroxypropyl derivative contents (Methocel-K3 and Methocel-E5) are used as biocompatible polymeric water-in-crude oil demulsifiers. Screening bottle tests revealed that Walocel and Methocel-E5 are more suitable for deionized water-in-crude oil demulsification. Better performance of Methocel-E5 compared to that of Methocel-K3 is due to comparative abundance of methyl substitutes in Methocel-E5 which assist interaction with oil. Further demulsification experiments at different temperatures and demulsifier concentrations confirmed that Walocel is comparatively more effective than Methocel-E5 for deionized water- and saline-in-crude oil demulsification. An increase in temperature/demulsifier concentration favor demulsification via increasing the number of effective collisions between emulsified water droplets which destabilize the emulsion. Presence of ions slows down the demulsification of Methocel E5 more than that of Walocel. Better performance of Walocel is probably due to the abundance and strength of its directional hydrogen bonds as well as electrostatic and van der Waals interactions with water via its charged carboxy groups which are less affected by ion content of saline; thus, relatively retain their ability to weaken asphaltene- and resins-assisted water interaction with crude oil. The polar 2-hydroxypropyl substitutes in Methocel E5 provides comparatively reduced number/strength of hydrogen bonds as well as relatively weak van der Waals interactions with water molecules which are more severely affected by shielding impact of ions resulting in much less effective saline demulsification with Methocel E5.