The development of concentrated and highly stable oil-in-water (O/W) emulsion is considered to be a cost-effective alternative for the transportation of produced heavy crude oils. However, the demulsification of a transported O/W emulsion is necessary once it reaches the destination. This article experimentally investigates the performance of four low-cost chemicals of varying water solubility as potential demulsifiers, independently and in combinations, for demulsifying two Indian heavy crude O/W emulsions prepared for pipeline transportation. The chemical demulsifiers used, in order of their higher water solubility, are: polyethylene glycol 400 (PEG) > polyoxyethylene (20) sorbitan monooleate (Tween-80) > linear alkylbenzene sulfonic acid (LABSA) > n-octylamine (OA). For this study, stable O/W emulsions (in the 60:40 ratio) of two Indian heavy crude oils were prepared using high-frequency ultrasonic waves in the presence of Triton X-100 as a surfactant. Both crude oils were characterized at first based on their physicochemical properties, infrared (IR) spectrum, and rheological properties. Prepared O/W emulsions were characterized based on rheological properties and droplet size. A bottle test method with heating (using a water bath) and enhanced gravity (by centrifuge) has been used to study the demulsification efficiency of used chemicals. Complete demulsification of both emulsions was achieved as desired. The synergetic effect of the interaction between two suitable demulsifiers provided remarkably better performance than that of independent returns, leading to minimization of the amount of demulsifier and the energy requirement for complete demulsification of both emulsions.