BackgroundPatients with multiple myeloma (MM) are often treated with chemotherapy, radiation, and, if indicated, autologous stem cell transplant. In addition to side effects of the treatment, patients with MM often have bone pain, pathological fractures, spinal cord compressions, fatigue, and muscle weakness, which negatively impact functional performance and quality of life. Currently, there are no related guidelines for safe and effective physiotherapy (PT) management. Accordingly, the aim of the present study is to develop guidelines for effective physiotherapy management of patients with MM by systematically reviewing and evaluating the available evidence followed by a consensus process to specifically describe the research questions as detailed below.Methods/designPhysiotherapy management guidelines for patients with multiple myeloma will be developed based on the results of a systematic search of the following databases: US National Library of Medicine Database (PubMed), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Elton B. Stephens Co. (EBSCO), Web of Science, Database of Abstracts of Reviews of Effects (DARE), Cochrane Database of Systematic Review, and Physiotherapy Evidence Database (PEDro). All articles will be screened for inclusion and exclusion criteria. Relevant potential articles will be identified and systematically reviewed for final phase of inclusion. Two independent reviewers will systematically review and analyze the quality of identified articles using standardized assessment tools. Scientific conclusions will be drawn and recommendations will be made based on a critical appraisal process. The guideline development will also be based on the team’s judgment about the overall quality of the studies and a consensus process.DiscussionDraft guidelines will be developed in the form of action statements based on the strength of evidence and grades of recommendations. The draft guidelines will be reviewed internally by two independent reviewers using AGREE II and externally by a methodological expert from Evidence-Based Care – Cancer Care Ontario and will be sent to the Canadian Physiotherapy Association (CPA) for feedback from physiotherapists.Systematic review registrationPROSPERO CRD42017064056Electronic supplementary materialThe online version of this article (10.1186/s13643-018-0785-7) contains supplementary material, which is available to authorized users.