<p>Biohybrid microrobots integrate biological components with synthetic structures to navigate complex biological environments, for example, for the delivery of drugs, microsurgery and in vivo diagnostics. In this Review, we propose a biophysics-informed design framework for biohybrid microrobots by connecting biophysical principles with biohybrid solutions. We first identify the biophysical constraints imposed by the human body that limit microrobot integrity, locomotion, navigation and functionality. We then examine the biophysical mechanisms through which biological cells, microorganisms and their derivatives adapt to these challenges, and explore how these can be utilized to improve the performance of microrobots. Building on these insights, we describe how biohybrid microrobots translate biophysical strategies into engineering solutions across four design domains: deformation, actuation, navigation and programming. Finally, we discuss persisting in vivo challenges, key considerations for clinical translation and future developments. By articulating design logics that span biological and synthetic domains, this framework provides a functional definition of biohybrid microrobots and offers a shared language for researchers across disciplines.</p>