In the face of today’s ever-evolving global health landscape and ambient assisted living (AAL), marked by the persistent emergence of novel viruses and diseases that impact vulnerable categories and individual safety, the need for innovative disinfection solutions has surged to unprecedented levels. In pursuit of advancing the field of autonomous UV-C disinfection robotics, we conducted two comprehensive state-of-the-art analyses: the first one in the literature and the second one in existing commercial disinfection robots to identify current challenges. Of all of the challenges, we consider the most outstanding ones to be safeguarding humans and animals and understanding the surroundings while operating the disinfection process challenges that we will address in this article. While UV-C lamps have demonstrated their effectiveness in sterilizing air and surfaces, the field of autonomous UV-C disinfection robotics represents a critical domain that requires advancement, particularly in safeguarding the wellbeing of humans and animals during operation. Operating UV-C disinfection robots in close proximity to humans or animals introduces inherent risks, and existing disinfection robots often fall short in incorporating advanced safety systems. In response to these challenges, we propose the RoboCoV Cleaner—an indoor autonomous UV-C disinfection robot equipped with an advanced dual and redundant safety system. This novel approach incorporates multiple passive infrared (PIR) sensors and AI object detection on a 360-degree camera. Under our test, the dual-redundant system reached more than 90% when detecting humans with high accuracy using the AI system 99% up to 30 m away in a university hallway (different light conditions) combined with the PIR system (with lower accuracy). The PIR system was proved to be a redundant system for uninterrupted operation during communication challenges, ensuring continuous sensor information collection with a swift response time of 50 ms (image processing within 200 ms). It empowers the robot to detect and react to human presence, even under challenging conditions, such as when individuals wear masks, in complete darkness, under UV light, or in environments with blurred visual conditions. In our test, the detection system performed outstandingly well with up to 99% detection rate of humans. Beyond safety features, the RoboCoV Cleaner can identify objects in its surroundings. This capability empowers the robot to discern objects affected by UV-C light, enabling it to apply specialized rules for targeted disinfection. The proposed system exhibits a wide range of capabilities beyond its core purpose of disinfection, making it suitable for healthcare facilities, universities, conference venues, and hospitals. Its implementation has the ability to improve significantly human safety and protect people. By showcasing the RoboCoV Cleaner’s safety-first approach and adaptability, we aim to set a new benchmark for UV-C disinfection robots, promoting clean and secure environments while protecting vulnerable people, even in challenging scenarios.