###### Abstract  
This systematic review and meta-analysis aimed to determine whether manual therapy (MT) and strengthening exercises (SE) reduce pain in patients with knee osteoarthritis (KO). Clinical trials were identified through a search of PubMed, PEDro, Scopus, and Ovid databases up to April 2024. Two independent reviewers screened articles, removing duplicates, and conducted full-text evaluations. Nineteen studies were included, with eight incorporated into the meta-analysis. Of these, seven addressed MT and twelve focused on SE. Although the studies included a variety of outcomes and follow-up periods, both interventions were shown to reduce pain immediately after the intervention, with MT providing superior short-term outcomes. Improvements were noted in the VAS scale for the MT group (effect size = 0.799; \(Z\) = 2.495; \(p\) = 0.013; IC 95%= 0.171 to 1.427; Q-value = 17.721; \(p\) = 0.001) and in the WOMAC pain score for the SE compared to controls (effect size = 0.364; \(Z\) = 1.993; \(p\) = 0.046; IC 95%= 0.006 to 0.722; Q-value = 2.4; \(p\) = 0.301). Both results showed high evidence according to GRADE. However, long-term effects are inconclusive, with low/very low levels of evidence. Both MT and SE are effective interventions in reducing pain in the short term. However, more clinical trials are needed to determine the best doses and the long-term effects. p <conceptsignificant impairment of mobility and quality of life of the patients [3]. However, these symptoms do not appear until joint degeneration has already progressed [4]. There are local and systemic risk factors. Local risk factors include obesity, previous unhealed injuries, congenital or acquired deformities, and malalignment in joint loads. Obesity is not only a mechanical factor, it also has a systemic impact, triggering alterations in the metabolism and homeostasis of joint tissues, leading to metabolism and homeostasis of joint tissues, which leads to the production of inflammatory substances that contribute to the development and progression of osteoarthritis [5]. Systemic risk factors include age, gender, race, hormones, diet, bone density, and genetics [6]. The incidence of the disease increases with age and is more common in women over the age of 50 [7]. Treatment of KO aims to reduce pain and inflammation and improve the function and quality of life of those affected, although there is currently no treatment that prevents KO [3]. There are conservative and non-conservative treatments [8; 9]. The main non-conservative treatment is the surgical replacement of the joint with a prosthesis, which is only used in the most advanced cases of KO because it is a high-risk treatment, especially in older people [10; 11]. Conservative treatment includes both pharmacological and non-pharmacological interventions (as lifestyle modifications, education, or physiotherapy), which are mainly used in the early stages of the disease [10]. Pharmacological treatment focuses mainly on non-steroidal anti-inflammatory drugs, which have shown limited pain relief and may have adverse effects, especially in elderly patients. Therefore, conservative non-pharmacological interventions are of great interest, as they can be prescribed to older patients without serious side effects. The best conservative non-pharmacological intervention is physiotherapy, which is a safe method that has been shown in several studies to be effective in reducing pain, increasing range of motion and improving function in patients with KO [12; 13; 14]. Thus, people suffering from KO should be provided with physiotherapy as part of their treatment [15]. Treatment focuses mainly on exercise and manual therapy (MT) [16; 17; 18]. However, there is no evidence as to which type of exercise may be most appropriate [19]. Regarding manual therapy, there are multiple interventions that are used in clinical practice in patients with KO, often in combination with exercise [14].