Fiber-based material systems are emerging as key elements for next-generation wearable devices due to their remarkable advantages, including large mechanical deformability, breathability, and high durability. Recently, greatly improved mechanical stability has been established in functional fiber systems by introducing atomic-thick two-dimensional (2D) materials. Further development of intelligent fibers that can respond to various external stimuli is strongly needed for versatile applications. In this work, helical-shaped semiconductive fibers capable of multifunctional sensing are obtained by wet-spinning MoS2 liquid crystal (LC) dispersions. The mechanical properties of the MoS2 fibers were improved by exploiting high-purity LC dispersions consisting of uniformly-sized MoS2 nanoflakes. Notably, three-dimensional (3D) helical fibers with structural chirality were successfully constructed by controlling the wet-spinning process parameters. The helical fibers exhibited multifunctional sensing characteristics, including (1) photodetection, (2) pH monitoring, (3) gas detection, and (4) 3D strain sensing. 2D materials with semiconducting properties as well as abundant surface reactive sites enable smart multifunctionalities in one-dimensional (1D) and helical fiber geometry, which is potentially useful for diverse applications such as wearable internet of things (IoT) devices and soft robotics.