Gastrointestinal (GI) tract diseases are responsible for substantial morbidity and mortality worldwide, including colorectal cancer, which has shown a rising incidence among adults younger than 50. Although this could be alleviated by regular screening, only a small percentage of those at risk are screened comprehensively, due to shortcomings in accuracy and patient acceptance. To address these challenges, we designed an artificial intelligence (AI)-empowered wireless video endoscopic capsule that surpasses the performance of the existing solutions by featuring, among others: (1) real-time image processing using onboard deep neural networks (DNN), (2) enhanced visualization of the mucous layer by deploying both white-light and narrow-band imaging, (3) on-the-go task modification and DNN update using over-the-air-programming and (4) bi-directional communication with patient’s personal electronic devices to report important findings. We tested our solution in an in vivo setting, by administrating our endoscopic capsule to a pig under general anesthesia. All novel features, successfully implemented on a single platform, were validated. Our study lays the groundwork for clinically implementing a new generation of endoscopic capsules, which will significantly improve early diagnosis of upper and lower GI tract diseases.