This systematic review and meta-analysis aimed to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the quality of life (QOL) and mental health (MH) of patients with cardiovascular disease (CVDs). Web of Science, Medline, Embase, Cochrane (CENTRAL), CINAHL, China National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal databases were searched from their date of establishment to July, 2023. A total of 5798 articles were screened, of which 25 were included according to the eligibility criteria. The weighted mean difference (WMD) and standardized mean difference (SMD) were used to analyze data from the same and different indicator categories, respectively. The fixed-effects model (FE) or random-effects model (RE) combined data based on the between-study heterogeneity. There were no statistically significant differences regarding QOL, physical component summary (PCS), mental component summary (MCS), and MH, including depression and anxiety levels, between the HIIT and MICT groups [SMD = 0.21, 95% confidence interval (CI) − 0.18–0.61, Z = 1.06, P = 0.290; SMD = 0.10, 95% CI − 0.03–0.23, Z = 1.52, P = 0.128; SMD = 0.07, 95% CI − 0.05–0.20, Z = 1.13, P = 0.25; SMD = − 0.08, 95% CI − 0.40–0.25, Z = − 0.46, P = 0.646; WMD = 0.14. 95% CI − 0.56–0.84, Z = 0.39, P = 0.694, respectively]. HIIT significantly improved PCS in the coronary artery disease (CAD) population subgroup relative to MICT. HIIT was also significantly superior to MICT for physical role, vitality, and social function. We conclude that HIIT and MICT have similar effects on QOL and MH in patients with CVD, while HIIT is favorable for improving patients’ self-perceived physiological functioning based on their status and social adjustment, and this effect is more significant in patients with CAD.