Objective: To systematically retrieve clinical practice guidelines in Chinese and English concerning the identification and management of post-stroke anxiety and depression, extracting the best available evidence for clinical implementation; to conduct a clinical status survey to understand the effectiveness, feasibility, and appropriateness of implementing this best evidence in practice, analyze barriers, and provide a reference for developing evidence-based nursing practice protocols for guideline-based identification and management of post-stroke anxiety and depression. Methods: Systematically retrieved clinical practice guidelines on the identification and management of post-stroke anxiety and depression in Chinese and English from databases including CNKI, Wanfang, VIP, CBM, PubMed, and relevant guideline websites such as RNAO, NZGG, NICE, SIGN, the Chinese Centre for Evidence-Based Medicine, and Yimaitong between January 2010 and December 2024. Employed the AGREE II tool to systematically evaluate the quality of screened guidelines, forming the best evidence suitable for clinical implementation. Through purposive sampling, seven nursing staff from neurology and neurosurgery departments and six stroke patients at a tertiary hospital were selected for semi-structured interviews to understand the current clinical implementation of post-stroke anxiety and depression identification and management, alongside patients’ psychological needs and experiences. Participatory observation was employed to examine departmental policies on stroke anxiety and depression care, identification and management practices, care documentation, and nursing staffing resources. Results: A literature search of relevant websites and databases yielded 1,088 articles. Following screening, six guidelines related to post-stroke anxiety and depression were ultimately included, excluding expert consensus and explanatory guidelines. Among these, three were international guidelines and three were domestic guidelines. Three project team members evaluated the guidelines using the AGREE II instrument, yielding ICC values of 0.901 (P < 0.001), 0.886 (P < 0.001), 0.811 (P < 0.001), 0.860 (P < 0.001), 0.834 (P < 0.001), and 0.905 (P < 0.001), respectively. All ICC values exceeded 0.75, indicating good inter-rater reliability. Among these, two guidelines achieved standardized scores exceeding 60% across all six domains, qualifying as Grade A quality. Two guidelines met ≥3 domains at ≥30% but had <60% in any domain, classifying as Grade B. Two guidelines had four domains below 30%, categorized as Grade C. Interview findings revealed a lack of established processes for identifying and managing post-stroke anxiety and depression within departments. Nursing staff demonstrated weak awareness and insufficient knowledge regarding the identification and management of post-stroke anxiety and depression. Patients commonly experienced anxiety and depression post-stroke, lacked key knowledge about stroke, and expressed a strong desire for nursing support. Conclusion: The included international guidelines on post-stroke anxiety and depression carried recommendations of Grade A and B, indicating overall high quality. In contrast, domestic guidelines carried recommendations of Grade B and C, reflecting generally moderate quality. International guidelines offer more comprehensive and detailed recommendations for identifying and managing post-stroke anxiety and depression than domestic guidelines. Domestic guidelines still lag behind international counterparts in terms of practicality, scientific rigor, and thoroughness. Consequently, China should actively explore localizing high-quality international guidelines to provide clinical nursing staff with evidence-based guidance for identifying and managing post-stroke anxiety and depression, thereby enhancing nursing service quality and evidence-based decision-making. Evidence-based nursing practice, grounded in optimal evidence from evidence-based guidelines, incorporates patient needs and preferences, professional nursing judgement, and the clinical context of evidence application to form final recommendation items. This provides guidance for identifying and managing post-stroke anxiety and depression in clinical settings, serving as the prerequisite and safeguard for translating optimal evidence into clinical transformation and application.