The objective of this systematic review and meta-analysis is to clarify the effect of exercise therapy on the first peak knee adduction moment (KAM), as well as other biomechanical loads in patients with knee osteoarthritis (OA), and identify physical characteristics that influence differences in biomechanical load after exercise therapy. The data sources are PubMed, PEDro, and CINAHL, from study inception to May 2021. The eligibility criteria include studies evaluating the first peak (KAM), peak knee flexion moment (KFM), maximal knee joint compression force (KCF), or co-contraction during walking before and after exercise therapy in patients with knee OA. The risk of bias was independently assessed by two reviewers using PEDro and NIH scales. Among 11 RCTs and nine non-RCTs, 1119 patients with knee OA were included (average age: 63.7 years). As the results of meta-analysis, exercise therapy tended to increase the first peak KAM (SMD 0.11; 95% CI: -0.03-0.24), peak KFM (SMD 0.13; 95% CI: -0.03-0.29), and maximal KCF (SMD 0.09; 95% CI -0.05-0.22). An increased first peak KAM was significantly associated with a larger improvement in knee muscle strength and WOMAC pain. However, the quality of evidence regarding the biomechanical loads was low-to-moderate according to the GRADE approach. The improvement in pain and knee muscle strength may mediate the increase in first peak KAM, suggesting difficulty in balancing symptom relief and biomechanical load reduction. Therefore, exercise therapy may satisfy both aspects simultaneously when combined with biomechanical interventions, such as a valgus knee brace or insoles. Registration: PROSPERO (CRD42021230966).