Background: Three-dimensional gait analysis, supported by advanced sensor systems, is a crucial component in the rehabilitation assessment of post-stroke hemiplegic patients. However, the sensor data generated from such analyses are often complex and challenging to interpret in clinical practice, requiring significant time and complicated procedures. The Gait Deviation Index (GDI) serves as a simplified metric for quantifying the severity of pathological gait. Although isokinetic dynamometry, utilizing sophisticated sensors, is widely employed in muscle function assessment and rehabilitation, its application in gait analysis remains underexplored. Objective: This study aims to investigate the use of sensor-acquired isokinetic muscle strength data, combined with machine learning techniques, to predict the GDI in hemiplegic patients. This study utilizes data captured from sensors embedded in the Biodex dynamometry system and the Vicon 3D motion capture system, highlighting the integration of sensor technology in clinical gait analysis. Methods: This study was a cross-sectional, observational study that included a cohort of 150 post-stroke hemiplegic patients. The sensor data included measurements such as peak torque, peak torque/body weight, maximum work of repeated actions, coefficient of variation, average power, total work, acceleration time, deceleration time, range of motion, and average peak torque for both flexor and extensor muscles on the affected side at three angular velocities (60°/s, 90°/s, and 120°/s) using the Biodex System 4 Pro. The GDI was calculated using data from a Vicon 3D motion capture system. This study employed four machine learning models—Lasso Regression, Random Forest (RF), Support Vector regression (SVR), and BP Neural Network—to model and validate the sensor data. Model performance was evaluated using mean squared error (MSE), the coefficient of determination (R2), and mean absolute error (MAE). SHapley Additive exPlanations (SHAP) analysis was used to enhance model interpretability. Results: The RF model outperformed others in predicting GDI, with an MSE of 16.18, an R2 of 0.89, and an MAE of 2.99. In contrast, the Lasso Regression model yielded an MSE of 22.29, an R2 of 0.85, and an MAE of 3.71. The SVR model had an MSE of 31.58, an R2 of 0.82, and an MAE of 7.68, while the BP Neural Network model exhibited the poorest performance with an MSE of 50.38, an R2 of 0.79, and an MAE of 9.59. SHAP analysis identified the maximum work of repeated actions of the extensor muscles at 60°/s and 120°/s as the most critical sensor-derived features for predicting GDI, underscoring the importance of muscle strength metrics at varying speeds in rehabilitation assessments. Conclusions: This study highlights the potential of integrating advanced sensor technology with machine learning techniques in the analysis of complex clinical data. The developed GDI prediction model, based on sensor-acquired isokinetic dynamometry data, offers a novel, streamlined, and effective tool for assessing rehabilitation progress in post-stroke hemiplegic patients, with promising implications for broader clinical application.