Bioelectronics, which converges biology and electronics, has attracted great attention due to their vital applications in human–machine interfaces. While traditional bioelectronic devices utilize nonliving organic and/or inorganic materials to achieve flexibility and stretchability, a biological mismatch is often encountered because human tissues are characterized not only by softness and stretchability but also by biodynamic and adaptive properties. Recently, a notable paradigm shift has emerged in bioelectronics, where living cells, and even viruses, modified via gene editing within synthetic biology, are used as core components in a new hybrid electronics paradigm. These devices are defined as “living synthelectronics,” and they offer enhanced potential for interfacing with human tissues at informational and substance exchange levels. In this Perspective, the recent advances in living synthelectronics are summarized. First, opportunities brought to electronics by synthetic biology are briefly introduced. Then, strategic approaches to designing and making electronic devices using living cells/viruses as the building blocks, sensing components, or power sources are reviewed. Finally, the challenges faced by living synthelectronics are raised. It is believed that this paradigm shift will significantly contribute to the real integration of bioelectronics with human tissues.