The giant dielectric behavior of CaCu 3 Ti 4 O 12 (CCTO) has been widely investigated owing to its potential applications in electronics; however, the loss tangent (tan δ ) of this material is too large for many applications. A partial substitution of CCTO ceramics with either Al 3+ or Ta 5+ ions generally results in poorer nonlinear properties and an associated increase in tan δ (to ~0.29–1.15). However, first-principles calculations showed that self-charge compensation occurs between these two dopant ions when co-doped into Ti 4+ sites, which can improve the electrical properties of the grain boundary (GB). Surprisingly, in this study, a greatly enhanced breakdown electric field (~200–6588 V/cm) and nonlinear coefficient (~4.8–15.2) with a significantly reduced tan δ (~0.010–0.036) were obtained by simultaneous partial substitution of CCTO with acceptor-donor (Al 3+ , Ta 5+ ) dopants to produce (Al 3+ , Ta 5+ )-CCTO ceramics. The reduced tan δ and improved nonlinear properties were attributed to the synergistic effects of the co-dopants in the doped CCTO structure. The significant reduction in the mean grain size of the (Al 3+ , Ta 5+ )-CCTO ceramics compared to pure CCTO was mainly because of the Ta 5+ ions. Accordingly, the increased GB density due to the reduced grain size and the larger Schottky barrier height ( Φ b ) at the GBs of the co-doped CCTO ceramics were the main reasons for the greatly increased GB resistance, improved nonlinear properties, and reduced tan δ values compared to pure and single-doped CCTO. In addition, high dielectric constant values ( ε ′ ≈ (0.52–2.7) × 10 4 ) were obtained. A fine-grained microstructure with highly insulating GBs was obtained by Ta 5+ doping, while co-doping with Ta 5+ and Al 3+ resulted in a high Φ b . The obtained results are expected to provide useful guidelines for developing new giant dielectric ceramics with excellent dielectric properties.