The lipid-α-Synuclein (α-Syn) interaction plays a crucial role in the pathogenesis of Parkinson’s disease. Here, we investigate the lipid-binding and -unbinding kinetics of α-Syn in an α-hemolysin (αHL) single nanopore. Under an applied voltage, an engineered α-Syn sequence can be trapped at the nanopore due to the dielectrophoretic force. The conformational switch events of α-Syn can be observed at the pore-membrane junction through the interpretation of blockade current amplitudes and dwell time. This allows further analysis of α-Syn conformational dynamics. We study how disease-associated metal ions (Cu²⁺, Zn²⁺) modulate the dynamics of α-Syn at the interface of the membranes and pore and how α-helical peptidomimetics stabilize the helical conformation of α-Syn in a lipidic environment. These studies aid our understanding of the complexity of the interaction of α-Syn, lipid membranes, and metal ions, and in using peptidomimetics, a new strategy against α-Syn toxicity and aggregation is advanced.