IntroductionDepression frequently affects patients with cardiovascular disease (CVD). When these conditions co-occur, outcomes such as quality of life and life expectancy worsen. In everyday practice, this specific and prevalent disease-disease interaction complicates patient management. Clinical practice guidelines (CPGs) aim to provide the best available advice for clinical decision-making to improve patient care. This study will aim to evaluate how CPGs specifically address depression in patients with CVD, and whether they provide any operational guidance for screening and management of depression in the primary care and outpatient setting.Methods and analysisWe will conduct a systematic review of CPGs on CVD management published from 2012 to 2023. A broad literature search for guidelines will be performed through electronic medical databases, grey literature search tools, and websites of national and professional medical organisations.Based on the inclusion criteria, two independent reviewers will evaluate eligible guidelines for screening and management recommendations on depression in patients with CVD. Additional points to be evaluated will be any mention of drug–drug or drug–disease interactions, other aspects of specific relevance to treating physicians, as well as general information on mental health. We will assess the quality of CPGs with a recommendation regarding depression in CVD patients using the Appraisal of Guidelines for Research and Evaluation II.Ethics and disseminationAs this systematic review is based on available published data, ethics approval and consent are not applicable. Our intent is that our results will be published in a peer-reviewed journal, presented at international scientific meetings, and distributed to healthcare providers.PROSPERO registration numberCRD42022384152.