In this paper, the investigation of a novel compact 2 × 2, 2 × 1, and 1 × 1 Ultra-Wide Band (UWB) based Multiple-Input Multiple-Output (MIMO) antenna with Defected Ground Structure (DGS) is employed. The proposed Electromagnetic Radiation Structures (ERS) is composed of multiple radiating elements. These MIMO antennas are designed and analyzed with and without DGS. The feeding is introduced by a microstrip-fed line to significantly moderate the radiating structure's overall size, which is 60 × 40 × 1 mm. The high directivity and divergence characteristics are attained by introducing the microstripfed lines perpendicular to each other. And the projected MIMO antenna structures are compared with others by using parameters like Return Loss (RL), Voltage Standing Wave Ratio (VSWR), Radiation Pattern (RP), radiation efficiency, and directivity. The same MIMO set-up is redesigned with DGS, and the resultant parameters are compared. Finally, the Multiple Input and Multiple Output Radiating Structures with and without DGS are compared for result considerations like RL, VSWR, RP, radiation efficiency, and directivity. This projected antenna displays an omnidirectional RP with moderate gain, which is highly recommended for human healthcare applications. By introducing the defected ground structure in bottom layer the lower cut-off frequencies of 2.3, 4.5 and 6.0 GHz are achieved with few biological effects on radio propagation in human body communications. The proposed design covers numerous well-known wireless standards, along with dual-function DGS slots, and it can be easily integrated into Wireless Body Area Networks (WBAN) in medical applications. This WBAN links the autonomous nodes that may be situated either in the clothes, on-body or beneath the skin of a person. This system typically advances the complete human body and the inter-connected nodes through a wireless communication channel.