Mirogabalin is a novel gabapentinoid drug, following gabapentin and pregabalin, and given as a first-line agent for peripheral neuropathic pain. Mirogabalin is a γ-aminobutyric acid analog that binds to the voltage-gated calcium channel subunit α₂δ1. However, the mirogabalin recognition mechanism of α₂δ1 remains elusive. Here we analyzed a structure of recombinant human α₂δ1 bound to mirogabalin at 3.88 Å resolution by cryo-electron microscopy. Our structure and mutagenesis binding assays confirmed that the evidence shown by others for gabapentinoid binding to a conserved amino acid binding motif located in the extracellular dCache_1 domain distal pocket applies to mirogabalin. In addition to the conserved residues interacting with the carboxyl and amino groups of mirogabalin, our mutagenesis binding assays newly identified residues W205 and Y217 in the hydrophobic interaction region are critical for mirogabalin binding. The A215L mutation, which was introduced to increase the side chain length at the hydrophobic interaction site of mirogabalin based on our structure, predictably suppressed the binding of mirogabalin while promoting the binding of another ligand, L-Leu, with a smaller hydrophobic substituent than mirogabalin. Our study indicates the significance of hydrophobic interactions in α₂δ1 mirogabalin recognition.