A resistive memory device including multiple resistive memory cells arranged in regions where first signal lines and second signal lines cross each other, and a method of operating the resistive memory device, are provided. The method includes applying a first voltage to a first line, from among unselected first signal lines connected to unselected memory cells, that is not adjacent to a selected first signal line connected to a selected memory cell from among the multiple memory cells; applying a second voltage that is lower than the first voltage to a second line, from among the unselected first signal lines, that is adjacent to the selected first signal line; floating the unselected first signal lines; and applying a third voltage that is higher than the first voltage to the selected first signal line.