In this paper, the theory of characteristic modes (TCM) is used for the first time to analyze the behavior of defected ground structures (DGS) when added to antenna designs. A properly designed DGS introduces currents opposite in direction to the original characteristic modes (CM) currents thus reducing mutual coupling. TCM is also applied to multiple-inputmultiple- output (MIMO) antenna systems to develop a systematic approach that can predict whether the isolation can be enhanced further or not. For this purpose two 4-element and one 2-element MIMO designs, i.e. monopole and planar inverted-F antennas (PIFA) are studied. The addition of different antenna elements affects the CM significantly as well as differently. Some of the CM excited on the antenna surface contribute to the coupling between the antenna ports that is why they can be classified as coupling modes. To improve the isolation, the DGS should be introduced at certain locations that blocks the coupling modes but at the same time does not affect the non-coupling modes. If their is no such location or the current on the surface of the chassis for coupling and non-coupling modes is approximately same, the isolation cannot be enhanced further. Using this approach, isolation was improved on an average by 11 dB in all the designs considered, giving the most isolation enhancement following a systematic way compared to other works.