In this paper, a novel microstrip line-fed meander-line-based four-elements quad band Multiple Input and Multiple Output (MIMO) antenna is proposed with a gain enhancement technique. The proposed structure resonates at four bands simultaneously, that is, 1.23, 2.45, 3.5 and 4.9 GHz, which resemble GPS L2, Wi-Fi, Wi-MAX and WLAN wireless application bands, respectively. The unit element is extended to four elements MIMO antenna structure exhibiting isolation of more than 22 dB between the adjacent elements without disturbing the resonant frequencies. In order to enhance the gain, two orthogonal microstrip lines are incorporated between the antenna elements which result in significant gain improvement over all the four resonances. Furthermore, the diversity performance of the MIMO structure is analyzed. The Envelope Co-Relation Coefficient (ECC), Diversity Gain (DG), Channel Capacity Loss (CCL), Mean Effective Gain (MEG) and Multiplexing Efficiency are obtained as 0.003, 10 dB, 0.0025 bps/Hz, −3 dB (almost) and 0.64 (min.), respectively, which are competent and compatible with practical wireless applications. The Total Active Reflection Coefficient (TARC) resembles the characteristic of the individual antenna elements. The layout area of the overall MIMO antenna is 0.33 λ × 0.29 λ, where λ is the free-space wavelength corresponding to the lowest resonance. The advantage of the proposed structure has been assessed by comparing it with previously reported MIMO structures based on number of antenna elements, isolation, gain, CCL and compactness. A prototype of the proposed MIMO structure is fabricated, and the measured results are found to be aligned with the simulated results.