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Objectives Weight loss through combined lifestyle interventions (CLIs) can slow down knee osteoarthritis (OA) progression. However, gender-related factors may influence both the implementation of and participation in CLIs. Therefore, the aims were to identify gender-related facilitators and barriers to CLI implementation among healthcare professionals (HCPs) and uptake and adherence among individuals with early-stage knee OA and overweight or obesity.Design Semi-structured interviews were conducted in this qualitative study. Thematic analysis, combining inductive and deductive approaches, was performed according to the Consolidated Framework for Implementation Research (CFIR) domains.Setting HCPs and individuals with knee OA and overweight or obesity were interviewed in Dutch between December 2023 and May 2024.Participants 16 HCPs who referred or delivered a CLI and 23 individuals with knee OA and overweight or obesity who participated in a CLI were purposively recruited. 16 participants identified themselves as women and 7 as men; no other gender identities were reported.Results HCPs experienced resistance to CLIs of both men and women. Additionally, HCPs perceived that women were more open and available to participate in CLIs, tended to prioritise others over themselves and often lacked familial support compared with men. Women valued trust, preferred female HCPs and struggled with self-prioritisation. Men were motivated by female HCPs and participants due to their empathy and interaction. Across men and women, barriers included conflicting HCP advice, work stress, caregiving tasks and lack of discipline, while social environment support was a key facilitator.Conclusions Addressing gender-related facilitators and barriers in the design and implementation of the CLI may improve long-term engagement and efficacy in individuals with knee OA and overweight or obesity.Trial registration number Overview of Medical Research in the Netherlands (OMON), managed by the CCMO: NL75367.078.20