A vehicle power supply system and a method for operating the same are provided. The vehicle power supply system includes a main battery and a sub-battery to supply power to an electronic load inside a vehicle, and a controller to control supplying of the power to the electronic load using at least one of the main battery or the sub-battery, by monitoring the main battery and the sub-battery. The controller determines whether the main battery allows entrance into Idle Stop and Go, determines whether the sub-battery is able to assist the ISG, and controls the sub-battery to assist the main battery to supply the power to the electronic load, when the main battery allows the entrance into the ISG, when the sub-battery is able to assist the ISG, and when entering into the ISG.