Confined spaces in the human body pose substantial challenges for biomedical procedures. Navigating these ultrasmall environments is essential for precise drug delivery, improving treatment outcomes and reducing adverse effects. Microrobots offer a promising approach to accessing these complex microenvironments. Here, we show a biohybrid microrobot based on picoeukaryotes, engineered as a cargo carrier for active delivery in tight in vivo spaces. The microrobot exhibits strong in vitro motility through narrow two-dimensional and complex three-dimensional networks and, in vivo, achieves outstanding kidney penetration, uniform distribution, and >48-hour retention while resisting flow shear and immune clearance, with excellent biosafety. Their ability to retain functionality and sustain propulsion within the confined and complex kidney vasculatures and interstitial spaces underscore their potential for long-term, active delivery in confined biological environments. The picoeukaryote-based biohybrid microrobot system represents a major advancement in active drug delivery, especially tailored to the challenging microenvironments of the kidney.