Silicon (Si)-based materials have a wide range of utilities in biophysical and biomedical research. Remotely-controlled Si configurations, however, are rarely explored due to a limited fundamental understanding of the complex physicochemical processes that occur at Si-biology interfaces. Here, we formulated a biology-guided rational design principle for establishing intra-, inter- and extracellular Si-based interfaces, where Si and biological targets have matched properties. We demonstrated the utility of these interfaces by showing light-controlled non-genetic modulations of intracellular calcium dynamics, cytoskeleton-based transport and structures, cellular excitability, and brain activities in vivo.