The prevention of diabetic foot ulcers remains a critical challenge. This study evaluates a smart compression sock designed to address this issue by integrating temperature, plantar pressure, and blood oxygen sensors and monitoring data recorded by these sensors. The smart sock, developed with input from a certified Pedorthist, was tested on 20 healthy adult participants aged 16 to 53. It includes four temperature sensors and pressure sensors at common ulcer sites (first and fifth metatarsal heads, calcaneus, and hallux), and a blood oxygen sensor on the hallux. The sensors are monitored, and their transduced data are collected and stored through an app installed on a personal cell phone. The mobile app interface is user-friendly, providing intuitive navigation and easy access to the sensors’ data. Using repeated measures ANOVA and post hoc tests, we analyzed the impact of various physical activities on physiological changes in the foot. The device effectively detected significant variations in blood oxygen, temperature, and pressure across six activities. Statistical analyses revealed significant differences based on activity type and sensor location. These results highlight the smart sock’s sensitivity and accuracy, suggesting its potential to prevent diabetic foot ulcers. Further clinical trials are needed to evaluate its efficacy in a larger, more diverse population.