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The objectives of this study were to assess the accuracy and precision of a system combining an IMU-instrumented sock and a validated algorithm for the estimation of the spatio-temporal parameters of gait. A total of 25 healthy participants (HP) and 21 patients with foot impairments secondary to psoriatic arthritis (PsA) performed treadmill walking at three different speeds and overground walking at a comfortable speed. HP performed the assessment over two sessions. The proposed system’s estimations of cadence (CAD), gait cycle duration (GCD), gait speed (GS), and stride length (SL) obtained for treadmill walking were validated versus those estimated with a motion capture system. The system was also compared with a well-established multi-IMU-based system for treadmill and overground walking. The results showed a good agreement between the motion capture system and the IMU-instrumented sock in estimating the spatio-temporal parameters during the treadmill walking at normal and fast speeds for both HP and PsA participants. The accuracy of GS and SL obtained from the IMU-instrumented sock was better compared to the established multi-IMU-based system in both groups. The precision (inter-session reliability) of the gait parameter estimations obtained from the IMU-instrumented sock was good to excellent for overground walking and treadmill walking at fast speeds, but moderate-to-good for slow and normal treadmill walking. The proposed IMU-instrumented sock offers a novel form factor addressing the wearability issues of IMUs and could potentially be used to measure spatio-temporal parameters under clinical conditions and free-living conditions.