In recent years, researchers have taken a keen interest in intelligent electrochemical interfaces. Nevertheless, incorporating multiple stimuli-responsive properties while ensuring a significant electrochemical response remains an interesting question. In this work, ligand-free gold nanoclusters grown on carbon nitride supports (AuNCs@N-C) were loaded on pyrolytic graphite (PG) electrode by layer-by-layer (LbL) method to obtain the {AuNCs@N-C}3 inner layers with good catalytic effect on isoquercitrin (IQ, 3-(β-d-Glucopyranosyloxy)-3′,4′,5,7-tetrahydroxyflavone). Then, the semi-penetrating stimuli-responsive hydrogel poly(N-isopropyl acrylamide)-poly(acrylic acid) (PNIPAM-PAA) was modified on the catalytic layer surface by drop-coating method. As a result, we obtained reversible electrochemical responses triggered by changes in temperature, sodium sulfate concentration, and pH. A new type of logic gate has been created by combining the difference in peak current during the stimulus response with the change in potential corresponding to the peak current. A 3-input/3-output tri-state buffer gate and a 1-to-4 demultiplexer have been designed through careful simplification, offering a fresh approach to building electrochemical pharmaceutical logic gates.