Introduction Effective antibiotic options in general practice for patients with infections are declining significantly due to antibiotic over-prescribing and emerging antibiotic resistance. To better improve antibiotic prescribing by general practitioner (GP), pharmacist-GP collaborations have been promoted under antibiotic stewardship programmes. However, there is insufficient information about whether and how pharmacists help GPs to more appropriately prescribe antibiotics. This systematic review aims to determine whether pharmacist-led or pharmacist-involved interventions are effective at improving antibiotic prescribing by GPs. Methods and analysis A systematic review of English language randomised controlled trials (RCTs), cluster RCTs, controlled before-and-after studies and interrupted time series studies cited in MEDLINE, EMBASE, EMCARE, CINAHL Plus, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials and Web of Science databases will be conducted. Studies will be included if a pharmacist is involved as the intervention provider and GPs are the intervention recipients in general practice setting. Data extraction and management will be conducted using Effective Practice and Organisation of Care data abstraction tools and a template for intervention description and replication. The Cochrane and ROBINS-I risk of bias assessment tools will be used to assess the methodological quality of studies. Primary outcome measures include changes (overall, broad spectrum and guidelines concordance) of GP-prescribed antibiotics. Secondary outcomes include quality of antibiotic prescribing, delayed antibiotic use, acceptability and feasibility of interventions. Meta-analysis for combined effect and forest plots, ‡ 2 test and I 2 statistics for detailed heterogeneity and sensitivity analysis will be performed if data permit. Grading of Recommendations Assessment, Development and Evaluation and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidance will be used to report findings. Ethics and dissemination No ethics approval is required as no primary, personal or confidential data are being collected in this study. The findings will be disseminated to national and international scientific sessions and published in a peer-reviewed journal. PROSPERO registration number CRD42017078478.