In the past decades, remarkable progress has been made in the field of human-machine interaction. The need for accurate sensing devices with satisfactory user experiences has propelled the development of flexible, stretchable, biocompatible, and imperceptible hydrogel-based interfaces. These innovative interfaces facilitate direct interactions between humans and machines while receiving detected input signals from sensors and giving output commands to controllers, thus motivating accurate real-time responsiveness. This Perspective discusses the sensing mechanisms for the two categories of hydrogel-based sensors and summarizes the recent progress in the development of different representations of human-machine interactions, including intelligent identification, information secrecy, interactive control, and virtual reality and augmented reality technologies. The advantages of hydrogel-based systems over conventionally used rigid electrical components are explicitly discussed. The conclusion provides a perspective on current challenges and outlines a future roadmap for the realization of state-of-the-art hydrogel-based smart systems.