As promising candidate for mid- and far-infrared (MFIR) nonlinear optical (NLO) materials, diamond-like (DL) chalcogenides have been extensively studied because of their considerable advantages. Among them, tellurides attract our attention as their stronger electron polarization and wider transmittance range than those of sulfides and selenides. Herein, the insightful structural characteristics and NLO properties of defect DL MGa2Te4 (M = Zn, Cd) were studied for the first time at experimental and theoretical level. They crystallize in the non-centrosymmetric I-4 space group (No.82), with a three-dimensional structure consisting of highly oriented [MTe4] and [GaTe4] tetrahedra, which can be viewed as derived from AgGaS2 (AGS). Experimental results illustrate that MGa2Te4 (M = Zn, Cd) exhibits moderate band gaps, strong SHG intensities about 4.9–10.6 times that of AGSe at 90–125 μm, and congruent-melting behavior. Theoretical calculations based on E-field DFPT method indicate that the tremendous SHG tensors d14 of ZnGa2Te4 and CdGa2Te4 are 127.67 and 105.19 pm/V. SHG-density analysis reveals that the lone-pair packets of Te ions in [GaTe4] units are the main source of SHG responses. In addition, calculations on Mulliken bond order index imply that the main difference between these two crystals is the bonding modes of M−Te. Special care was also given to ensure convergence of k-mesh for both conventional and primitive cells of the crystals, with two different methods for calculating linear and non-linear optical properties compared side by side. This work demonstrates the potential applications of these two defect DL tellurides in the MFIR NLO field.