Fluorosilicone surfactants integrate the advantages of fluorocarbon and organosilicone surfactants, resulting in desirable properties including enhanced surface activity and strong aggregation ability. In this study, a series of polyether-modified fluorosilicone (FSiPEs) was designed and synthesized. The structures of the parent hydrogenterminated fluorosilicone oil (FPH-5) and the FSiPEs were characterized using Fourier transform infrared spectroscopy and 1H, 13C, 29Si, and 13C-1H HSQC nuclear magnetic resonance spectroscopy. The surface activity, aggregation properties, wettability, and foam properties of FSiPEs in aqueous solution were investigated using surface tension, dynamic light scattering (DLS), transmission electron microscopy (TEM), and dynamic contact angle measurements. The FSiPEs exhibited high surface activity in aqueous solution and good wettability on lowenergy surfaces. In addition, the DLS and cryo-TEM results indicated that the FSiPEs can spontaneously form multilayer multicompartmental vesicles in aqueous solution. Consequently, these surfactants have potential applications in drug delivery and biofilm mimicry.