In this work, the Mg2Al4-x(Mg0.5Ti0.5)xSi5O18 (0 ≤ x ≤ 0.20) ceramics were successfully synthesized via the solid-state reaction. The main phase was Mg2Al4Si5O18 with an orthorhombic structure, and the secondary phases (SiO2, TiO2 and Al2SiO5) were formed during the synthesis of Mg2Al4-x(Mg0.5Ti0.5)xSi5O18 ceramics. The substitution of Al3+ by (Mg0.5Ti0.5)3+ occurs complex chemical reaction: Mg ions prefer to occupy the Mg-site deficiency in Mg2Al4Si5O18; Ti ions substitute Si-site at x < 0.12, whereas Ti ions also occupy Al-site and remaining to form TiO2 phase at x ≥ 0.12. The dielectric constant (εr), quality factor (Qf) and temperature coefficient of resonance frequency (τf) are mainly dominated by the ionic polarizability, relative density, secondary phases and bond valence of Mg-site. Additionally, the bond ionicity (fi) of Mg–O, lattice energy (U) of Si–O and bond energy (E) of Al–O also influence εr, Qf and τf, respectively. The moderate (Mg0.5Ti0.5)3+ ions substitution not only effectively improve Qf while maintaining low εr, but also reduce densification temperature. The excellent microwave dielectric properties with εr = 4.45, Qf = 33,995 GHz and τf = −39 ppm/°C were obtained in Mg2Al4-x(Mg0.5Ti0.5)xSi5O18 (x = 0.08) ceramic sintered at 1375 °C, which is potential for millimeter-wave communication.