In present study, high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics (x = 0.00–0.45) were synthesized using solid-state reaction route, which formed a single-phase spinel structure with a Fd-3m space group. The reduction in unit cell volume and lattice parameters were attributed to the compression of polyhedral structures. A moderate content of Li+ ions promoted the grain growth and improved the densification of ceramics. The internal connection among the conformational entropy (ΔSconfig), structure, and microwave dielectric properties in high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics was systematically studied. The dielectric constant (εr) was largely affected by the polarizability, and relatively high conformational entropy helped to increase the phonon vibrational energy and enhance the bond strength, resulting in low εr values. Additionally, the high concentration of oxygen vacancies, high packing fraction, low internal strain/fluctuation and suppressed damping behavior were closely related to relatively low conformational entropy. Notably, the introduction of oxygen vacancy leaded to the Al3+ ions preferentially occupy tetrahedral sites enhancing the covalency. These factors collectively reduced the intrinsic losses and improved the quality factor (Q×f). Moreover, relatively high conformational entropy conduced to the structural stability by improving the M-O (M = Li, Mg, Zn, Co, and Ni) bond strength and valence, which contributes to achieve near-zero temperature coefficient of resonant frequency (τf). As ΔSconfig changes, high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics presented great microwave dielectric properties: εr values of 5.46 ∼ 8.49, Q×f values of 3,540 GHz (f = 14.84 GHz) ∼ 56,950 GHz (f = 12.99 GHz), and τf values of −58 ppm/°C∼ −14 ppm/°C. Our study demonstrates that the high-entropy strategy effectively enhances microwave dielectric properties. This approach has potential applications across a broad spectrum of microwave dielectrics ceramics.