IntroductionKnee osteoarthritis is a chronic degenerative disease associated with significant chronic pain, disability and impaired quality of life and is the most common form of osteoarthritis. There is no cure for knee osteoarthritis, and the main therapeutic goals are pain management and improving quality of life. The objective of this study is to evaluate the relative efficacy and acceptability of available interventions using network meta-analysis (NMA) to provide a comprehensive evidence base to inform future treatment guidelines.Methods and analysisA comprehensive literature search of major electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) and clinical trial registries will identify randomised control trials (RCTs) of interventions listed in NICE guidelines for the treatment of knee osteoarthritis in adults. We will perform an NMA to estimate relative intervention effects across the whole treatment network. If any studies use multicomponent intervention packages, we will employ a component NMA model to estimate the contribution of individual components. The quality of evidence will be assessed using the Confidence in Network Meta-Analysis approach, which is based on the traditional GRADE framework adapted for NMA. Risk of bias (RoB) will be assessed using the revised Cochrane RoB 2.0 tool for RCTs.Ethics and disseminationThis study does not require ethical approval. Findings will be submitted to a peer-reviewed journal.PROSPERO registration numberCRD42020184192.