Piezoionic hydrogels offer a route to mechanically driven bioelectronic interfaces, but their output is limited by rapid, symmetric ion redistribution that dissipates charge gradients. In biological electrocytes, efficient signal generation arises from the coupling of ion selectivity with spatial confinement that regulates transport. Here, we introduce a confinement-connectivity design strategy for piezoionic hydrogels, implemented through a supramolecular poly(vinyl alcohol)-glycerol-cucurbit[5]uril (PVA-glycerol-CB[5]) mesoporous network with a layered Negative-Neutral-Positive architecture that simultaneously increases pore fraction while reducing characteristic pore size. This architecture constrains ionic redistribution while maintaining a large mobile-ion reservoir, enabling deformation-driven charge separation. Compression generates peak outputs of ~180 mV and ~9 mA and elicits synchronized electromyographic responses in the mouse sciatic nerve without external power. These results establish confinement-connectivity coupling, rather than bulk conductivity, as a materials design framework in which coupling pore connectivity and confinement governs piezoionic transduction.