Assistive powered wheelchairs will bring patients and elderly the ability of remain mobile without the direct intervention from caregivers. Vital signs from users can be collected and analyzed remotely to allow better disease prevention and proactive management of health and chronic conditions. This research proposes an autonomous wheelchair prototype system integrated with biophysical sensors based on Internet of Thing (IoT). A powered wheelchair system was developed with three biophysical sensors to collect, transmit and analysis users’ four vital signs to provide real-time feedback to users and clinicians. A user interface software embedded with the cloud artificial intelligence (AI) algorithms was developed for the data visualization and analysis. An improved data compression algorithm Minimalist, Adaptive and Streaming R-bit (O-MAS-R) was proposed to achieve a higher compression ratio with minimum 7.1%, maximum 45.25% compared with MAS algorithm during the data transmission. At the same time, the prototype wheelchair, accompanied with a smart-chair app, assimilates data from the onboard sensors and characteristics features within the surroundings in real-time to achieve the functions including obstruct laser scanning, autonomous localization, and point-to-point route planning and moving within a predefined area. In conclusion, the wheelchair prototype uses AI algorithms and navigation technology to help patients and elderly maintain their independent mobility and monitor their healthcare information in real-time.