The human voltage-gated sodium channel subtype 1.7 (hNaV1.7) is emerging as an attractive target for the development of potent and subtype selective novel analgesics with increased potency and fewer side effects than existing therapeutics. HwTx-IV, a spider derived peptide toxin, inhibits hNaV1.7 with high potency and is therefore of great interest as an analgesic lead. In the current study we characterized the membrane binding properties of HwTx-IV to determine whether increasing its interaction with lipid membranes would lead to an increase in the inhibitory potency of the peptide at hNaV1.7. HwTx-IV analogues [E1PyrE]HwTx-IV (mHwTx-IV) and [E1G,E4G,F6W,Y30W]HwTx-IV (gHwTx-IV) were studied, and their ability to bind to model membranes binding was compared to that of HwTx-IV. Whereas HwTx-IV and mHwTx-IV exhibited weak binding affinity for lipid membranes, gHwTx-IV showed improved affinity for the model membranes studied regardless of the overall charge or fluidity of the lipids used. Furthermore, our results suggest that gHwTx-IV binds superficially to the lipid bilayer surface through electrostatic and hydrophobic interactions. In addition, activity assays using SH-SY5Y neuroblastoma cells expressing hNaV1.7 showed that gHwTx-IV has increased activity at hNaV1.7 compared to HwTx-IV revealing that an increase in the affinity for lipid membranes improves HwTx-IV potency. The correlation between membrane interactions and hNaV1.7 inhibition was explored using a range of biophysical techniques including computational analysis, surface plasmon resonance, fluorescence spectroscopy and fluorescence imaging plate reader activity assays on HwTx-IV and the two analogues. Our results suggest that gHwTx-IV interacts with the lipid membrane via electrostatic interactions before binding to the channel and we hypothesize that increasing the affinity of gating modifier toxins to lipid bilayers is a strategy that may be useful for improving their potency at hNaV1.7.