Abstract: Traditional laminates are usually made up of plies with 0°, 45°, −45°, and 90°(Quad). However, the Quad layup has limited design space for stiffness, and the excessive arrangement sequence makes ply optimization and thickness reduction design exceptionally difficult. The Double-Double (DD) laminate, based on the invariance of the Tsai modulus, provided an alternative method to traditional layup. It held promise for simplifying the design process of laminate layups and structures. Currently, research for DD laminates primarily focused on the single carbon fiber types, while further research is needed for hybrid laminate configurations. To extend the design of DD laminates to hybrid conditions, the normalized stiffness and equivalent replacement for hybrid DD laminates were investigated based on the invariance of the Tsai modulus. Experimental verification confirmed the feasibility of ply replacement for hybrid DD laminates and their advantages in thickness reduction design. The results indicated that the normalized stiffness of hybrid DD laminates followed the hybrid law with respect to the Tsai modulus hybrid proportion p^*. The layup parameters V and allowable range for equivalent replacement of hybrid DD laminates were influenced by the hybrid proportion and fiber types. A hybrid DD layup strategy with higher homogeneity can be achieved through a repeated configuration +Φ_g/−Ψ_c/+Ψ_c/−Φ_gr (tension-bending consistency) or a symmetric configuration or ±Φ_g /±Ψ_cS (no coupling effect). Tensile experimental results for the equivalent layup of hybrid carbon fiber/glass fiber quasi-isotropic laminates indicated that hybrid DD laminates and their reduced-thickness configurations could achieve equivalent tensile stiffness substitution (error < 3%), while tensile strength was influenced by specific configurations and failure modes (error ranging from −15.2% to +2.1%). This demonstrates the feasibility of equivalent ply substitution for hybrid DD laminates and provides a new approach for the design of hybrid laminates.