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In this study, the effects of different soluble proteins, including collagen peptides (CP), soy protein hydrolysate (HSPI), whey protein isolate (WPI), sodium caseinate (SC), and egg white protein (EWP), on the structural and mechanical properties of blends containing soy protein isolate (SPI) and wheat gluten (WG) were investigated using high-moisture extrusion. The addition of CP and HSPI resulted in a more pronounced fibrous structure with increased voids, attributing to their plasticizing effect that enhanced polymer chain mobility and reduced viscosity. WPI, SC, and EWP acted as crosslinking agents, causing early crosslink formation and decreased polymer chain mobility. These structural variations directly influenced the tensile properties of the extrudates, with CP displaying the highest anisotropic index. Moreover, the presence of soluble proteins impacts the permeability of the extrudates. These insights shed light on how soluble proteins can be used to modify the properties of SPI-WG blends, making them suitable for meat analogue production.