Background Knee osteoarthritis (OA) remains a leading aetiology of disability worldwide. Clinical assessment of such knee-related conditions has improved with recent advances in gait analysis. Despite being a gold standard method, gait data acquired by motion capture (mocap) technology are highly non-linear and dimensional, which make traditional gait analysis challenging. Thus, extrinsic algorithms need to be used to make sense of gait data. Supervised Machine Learning (ML)-based classifiers outperform conventional statistical methods in revealing intrinsic patterns that can discern gait abnormalities when using mocap data, making them a suitable tool for aiding diagnosis of knee OA. Research question Studies have demonstrated the accuracy of supervised ML-based classifiers in gait analysis. However, these techniques have not gained wide acceptance amongst biomechanists for two reasons: the reliability of such methods has not been assessed and there is no consensus on which classifier or group of classifiers to select. Specifically, it is not clear whether classifiers that leverage optimal separating hyperplanes (OSH) or artificial neural networks (ANN) are more accurate and reliable. Methods A systematic review and meta-analysis were conducted to assess the capability of such algorithms to predict pathological kinematic and kinetic gait patterns as indicators of knee OA. With 153 eligible studies, 6 studies met the inclusion criteria for a subsequent meta-analysis, accounting for 273 healthy subjects and 313 patientswith symptomatic knee OA. The classification performance of supervised ML classifiers (OSH- or ANN-based) used in these studies was quantitatively assessed and compared across four following performance metrics: classification accuracy on the test set (ACC), sensitivity (SN), specificity (SP), and area under the receiver operating characteristic curve (AUC). Results There was no statistically significant discrepancy in the ACC between OSH- and ANN-based classifiers when dealing with kinetic and kinematic data concurrently, as well as when considering only kinematic data. However, there was a statistically significant difference in their SN and SP, with the ANN-based classifiers having higher SN and SP than OSH-based algorithms. As only one of the eligible studies reported AUC, this metric could not be assessed statistically across studies. Significance This study supports the use of ANN-based algorithms for classifying knee OA-related gait patterns as having a higher sensitivity and specificity than OSH-based classifiers. Considering their higher reliability, leveraging supervised ANN-based methods can aid biomechanists to diagnose knee OA objectively.