Clinical guidelines need high-quality studies to support clinical decision making, in which the evidence often was collected from systematic reviews (SRs) and/or meta-analyses (MAs). At present, the methodological quality and risk of bias (RoB) of SRs/MAs on stem cell therapy for the treatment of knee osteoarthritis (KOA) has been poorly investigated. This study aims to strictly evaluate the methodological quality and RoB in SRs/MAs of stem cell therapy for KOA. Four electronic databases (PubMed, Embase, Cochrane Library, and Web of Science databases) were searched, from inception to October 5, 2021. SRs/MAs involving randomized control trials or cohort studies on stem cell therapy for the treatment of KOA were included. The methodological quality and RoB were assessed using AMSTAR 2 and ROBIS tool, respectively. In total, 22 SRs/MAs were included. According to the results obtained by AMSTAR 2 tool, all SRs/MAs were rated as "Critically low." Main methodological weaknesses were as follows: up to 81.82% did not meet protocol registration requirements, only 13.64% provided a list of excluded studies and justification, and 13.64% investigated and discussed the publication bias. ROBIS-based RoB assessment showed that all the SRs/MAs were rated as "High." Besides, the lack of following the implementation of the PRISMA reporting guideline seems to reduce the methodological quality of the studies. The overall methodological quality of the SRs/MAs concerning the application of stem cell therapy in treating KOA is "Critically low," while the RoB is high. It is difficult to provide effective evidence for the formulation of guidelines for KOA treatment. We suggest that the relevant methodological quality assessment should be carried out in the future before the SRs/MAs are used as clinical evidence. In addition, it may be necessary for many journals to include the checklist with a submitted article. PROSPERO registration number: CRD42021246924.