AbstractTension in cell membranes is closely related to various cellular events, including cell movement and morphogenesis. Therefore, modulation of membrane tension can be a new approach for manipulating cellular events. Here, we show that an amphipathic peptide derived from the influenza M2 protein (M2[45–62]) yields lamellipodia at multiple sites in the cell. Effect of M2[45–62] on cell membrane tension was evaluated by optical tweezer. The membrane tension sensor protein FBP17 was involved in M2[45–62]-driven lamellipodium formation. Lysine-to-arginine substitution in M2[45–62] further enhanced its activity of lamellipodium formation. M2[45–62] had an ability to reduce cell motility, evaluated by scratch wound migration and transwell migration assays. An increase in neurite outgrowth was also observed after treatment with M2[45–62]. The above results suggest the potential of M2[45–62] to modulate cell movement and morphology by modulating cell membrane tension.