Objective To synthesize evidence related to management models for polypharmacy in home-dwelling older adults with chronic diseases and to enhance the safety of polypharmacy. Methods A systematic search was conducted in domestic and international professional websites and databases for literature concerning management models for polypharmacy in this population.Relevant evidence was extracted after literature screening and methodological quality assessment. Results A total of 14 articles were included.Thirty-five pieces of evidence were summarized across 13 dimensions, including nursing models, interactive assessment, medication review, deprescribing, health record establishment, multidisciplinary collaboration, interagency coordination, patient/caregiver involvement, personalized treatment management, education and follow-up, telecare, policy support, and continuing education for medical staff. Conclusion The synthesized evidence on management models for polypharmacy in home-dwelling older adults with chronic diseases can provide an evidence-based foundation for healthcare professionals in primary care settings, patients, and family caregivers, thereby improving medication safety.