This article developed a novel real-time control approach for the sparse and safe frequency regulation in inverter intensive microgrids (MGs). In the scenario, the inverters and external grids are expected to be synchronized with a desired frequency. To this end, the active power set-point acting as a control from a high-level controller is designed while considering two important performance metrics, namely “sparsity” and “safety”, which are to reduce the information exchange between controllers and ensure that the frequency remains in safe regions during the whole operation process. Our proposed control design framework allows the sparse linear feedback controller (SLFC) to be unified with a family of conditions for safe control using control barrier functions. A quadratic programming (QP) problem is then constructed, and the real-time control policy is obtained by solving the QP problem. Further, we also found that the proposed real-time control depends on the cross-layer communication network topology, which is the union of the one between controllers from SLFC and that determined by the power flow network. The proposed control approach has been validated through extensive case studies.