Abstract: Based on evidence-based medicine, this guideline aims to construct a multidisciplinary and standardized diagnostic and treatment framework for the complex bidirectional relationship between depressive disorder and cardiovascular and cerebrovascular diseases (CCVD). A total of 42 experts from psychiatry, cardiology, psychology, public health and evidence-based medicine participated in the consensus process. Clinical questions were formulated according to the population, intervention, comparison, and outcomes (PICO) principle. The grading of recommendations assessment, development, and evaluation (GRADE) system was employed for evidence certainty grading and recommendation strength evaluation, with consensus reached through two rounds of modified Delphi method and anonymous voting. The guideline provides 10 core recommendations, covering 4 aspects. (1) Screening and assessment: baseline metabolic monitoring and patient health questionnaire-9 (PHQ-9) screening are recommended at the initial point of care. (2) Antidepressants: selective serotonin reuptake inhibitors (SSRI) with favorable cardiovascular safety such as escitalopram are strongly recommended as first-line treatment; it is weakly recommended to use serotonin–norepinephrine reuptake inhibitors (SNRI) such as duloxetine and venlafaxine and blood pressure should be monitored dynamically; tricyclic antidepressants (TCA) with significant cardiac side effects are strongly not recommended. (3) Non-pharmacological interventions: cognitive behavioral therapy (CBT), mindfulness-based therapy, and lifestyle management are strongly recommended; repetitive transcranial magnetic stimulation (rTMS) and aerobic exercise are weakly recommended. (4) Comprehensive management: it is emphasized that on the basis of conventional CCVD treatment, efforts should be made to actively prevent and control the risk of bleeding or arrhythmia caused by drug interactions. This guideline emphasizes multidisciplinary collaboration and individualized comprehensive interventions, aiming to optimize the clinical decision-making process for comorbid depression and CCVD, and to improve the social function and long-term prognosis of patients.