Background Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and significantly impact patients’ quality of life (QoL) and mental health. A healthy lifestyle has been recognized as an essential factor in reducing the burden of CVD and improving patient outcomes. This study aimed to investigate the relationship between the Healthy Lifestyle Index and QoL and depression among patients with CVD. Methods and materials This descriptive-analytical cross-sectional study was conducted in 2024 among 182 patients with confirmed CVD who were referred to Imam Khomeini Hospital in Tehran. Data were collected using three validated instruments: a demographic questionnaire, the Short Form-12 Health Survey (SF-12) to assess QoL, and the Patient Health Questionnaire-9 (PHQ-9) to measure depression. The Healthy Lifestyle Index included physical activity, dietary habits, smoking, alcohol use, and social interaction. Generalized linear models were used to examine the associations between lifestyle components and outcomes (QoL and depression), adjusting for key confounders. All statistical analyses were performed using SPSS software version 22. Results The findings showed that the mean SF-12 QoL score among participants was 84.29 (SD = 7.53), and the mean age was 59.54 years (SD = 11.73). Physically active patients had significantly higher QoL scores (mean = 88.3) compared to inactive individuals (mean = 82.1) (P < 0.001). Greater social interaction was also associated with better QoL (mean = 87.9 vs. 80.4, P < 0.001). In contrast, alcohol consumption was associated with lower QoL (mean = 79.2 vs. 85.1, P = 0.04). Smoking status, BMI, and healthy eating score were not significantly related to QoL. Moreover, participants with higher Healthy Lifestyle Index scores had lower depression scores (mean PHQ-9 = 5.2 vs. 8.7, P < 0.01). Conclusion The results highlight the importance of promoting physical activity, reducing alcohol consumption, and encouraging social engagement as key components of healthy lifestyle interventions for patients with CVD. These strategies may effectively improve QoL and reduce depressive symptoms, underscoring the need for holistic and behaviorally focused approaches in the routine care of cardiovascular patients.

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