Engineered oral microbiota offer a promising approach for the prevention and treatment of cardiovascular diseases (CVDs). The oral microbiome, the second largest microbial habitat in the human body, plays a critical role in maintaining oral health and is closely linked to systemic diseases, including CVDs. Dysbiosis of the oral microbiota has been associated with conditions such as periodontitis, which can contribute to atherosclerosis and other CVDs. Engineered bacteria can be designed to produce beneficial metabolites, regulate glucose metabolism, reduce inflammation, and modulate the microbiota to improve cardiovascular health. Recent advances in synthetic biology have enabled the precise engineering of bacteria to target specific CVD risk factors, such as obesity, hyperlipidemia, diabetes, and inflammatory bowel disease. Engineered probiotics, such as genetically modified Lactobacillus and Escherichia coli strains, can secrete bioactive molecules like GLP-1, which regulate metabolism and reduce blood pressure. Additionally, engineered oral pathogens can be modified to reduce their harmful effects, such as by inhibiting biofilm formation in Streptococcus mutans. The potential of engineered oral microbiota in CVD treatment is supported by studies showing that engineered bacteria can improve cardiovascular outcomes, including reducing atherosclerosis, enhancing cardiac function, and modulating inflammatory responses. However, challenges remain, including ensuring the safety and stability of engineered bacteria, as well as optimizing their delivery and efficacy. Future research should focus on developing more stable and effective engineered microbiota, improving clinical applications, and addressing regulatory and ethical considerations. This review highlights the growing potential of engineered oral microbiota in CVD treatment and emphasizes the need for further research to translate these findings into clinical practice. The integration of synthetic biology with microbiome research offers a promising avenue for personalized and targeted therapies for CVDs.Engineered oral microbiota offer a promising approach for the prevention and treatment of cardiovascular diseases (CVDs). The oral microbiome, the second largest microbial habitat in the human body, plays a critical role in maintaining oral health and is closely linked to systemic diseases, including CVDs. Dysbiosis of the oral microbiota has been associated with conditions such as periodontitis, which can contribute to atherosclerosis and other CVDs. Engineered bacteria can be designed to produce beneficial metabolites, regulate glucose metabolism, reduce inflammation, and modulate the microbiota to improve cardiovascular health. Recent advances in synthetic biology have enabled the precise engineering of bacteria to target specific CVD risk factors, such as obesity, hyperlipidemia, diabetes, and inflammatory bowel disease. Engineered probiotics, such as genetically modified Lactobacillus and Escherichia coli strains, can secrete bioactive molecules like GLP-1, which regulate metabolism and reduce blood pressure. Additionally, engineered oral pathogens can be modified to reduce their harmful effects, such as by inhibiting biofilm formation in Streptococcus mutans. The potential of engineered oral microbiota in CVD treatment is supported by studies showing that engineered bacteria can improve cardiovascular outcomes, including reducing atherosclerosis, enhancing cardiac function, and modulating inflammatory responses. However, challenges remain, including ensuring the safety and stability of engineered bacteria, as well as optimizing their delivery and efficacy. Future research should focus on developing more stable and effective engineered microbiota, improving clinical applications, and addressing regulatory and ethical considerations. This review highlights the growing potential of engineered oral microbiota in CVD treatment and emphasizes the need for further research to translate these findings into clinical practice. The integration of synthetic biology with microbiome research offers a promising avenue for personalized and targeted therapies for CVDs.