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 the modified Delphi method and anonymous voting. The guideline provides 10 core recommendations including 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; serotonin–norepinephrine reuptake inhibitors (SNRI) such as duloxetine and venlafaxine are weakly recommended with dynamic blood pressure monitoring; 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: the prevention of drug interactions causing bleeding or arrhythmia within routine CCVD care is emphasized. This guide emphasizes that multidisciplinary collaboration and individualized interventions are essential to optimizing clinical decision-making and improving the social functioning and long-term prognosis of these patients.