AbstractIn this paper, we address high performance extreme‐scale molecular dynamics (MD) algorithm in the GENESIS software to perform cellular‐scale molecular dynamics (MD) simulations with more than 100,000 CPU cores. It includes (1) the new algorithm of real‐space nonbonded interactions maximizing the performance on ARM CPU architecture, (2) reciprocal‐space nonbonded interactions minimizing communicational cost, (3) accurate temperature/pressure evaluations that allows a large time step, and (4) effective parallel file inputs/outputs (I/O) for MD simulations of extremely huge systems. The largest system that contains 1.6 billion atoms was simulated using MD with a performance of 8.30 ns/day on Fugaku supercomputer. It extends the available size and time of MD simulations to answer unresolved questions of biomacromolecules in a living cell.