The article "Cardiovascular Disease Therapeutics via Engineered Oral Microbiota: Applications and Perspective" explores the role of the oral microbiome in cardiovascular diseases (CVDs) and the potential of engineered oral microbiota as a therapeutic approach. CVDs, the leading cause of death globally, are linked to systemic metabolic conditions such as obesity, hyperlipidemia, diabetes, and inflammatory bowel disease (IBD). The oral microbiome, the second largest microbial community in the human body, plays a crucial role in maintaining microbial homeostasis and can contribute to the onset or progression of CVDs through dysbiosis. The authors discuss the association between oral microbiota and CVDs, highlighting how periodontal diseases can lead to systemic inflammation and contribute to atherosclerosis. The article outlines the application of engineered bacteria in treating CVDs, including obesity, hyperlipidemia, diabetes, and IBD. Genetically modified bacteria can express beneficial traits such as N-acylphosphatidylethanolamines to resist obesity, secrete antioxidants to prevent liver oxidative damage, and produce glucagon-like peptide-1 (GLP-1) to regulate glucose metabolism and reduce blood pressure. The use of synthetic biology tools allows for precise control over bacterial interactions with the host, enhancing the effectiveness and safety of these therapies. The potential of engineered oral probiotics and pathogenic bacteria is also discussed, emphasizing the versatility of the oral microbiome as a target for microbial engineering. Oral probiotics like *Lactobacillus* strains can be engineered to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues. Oral pathogens associated with CVDs can be modified through protein and genetic engineering to reduce their virulence and promote beneficial effects. Despite the promising prospects, the authors acknowledge challenges such as bacterial virulence, genetic instability, and the need for regulatory compliance. They highlight the importance of continued research and technological advancements to overcome these hurdles and develop more effective and safe engineered oral microbiota therapies for CVDs.The article "Cardiovascular Disease Therapeutics via Engineered Oral Microbiota: Applications and Perspective" explores the role of the oral microbiome in cardiovascular diseases (CVDs) and the potential of engineered oral microbiota as a therapeutic approach. CVDs, the leading cause of death globally, are linked to systemic metabolic conditions such as obesity, hyperlipidemia, diabetes, and inflammatory bowel disease (IBD). The oral microbiome, the second largest microbial community in the human body, plays a crucial role in maintaining microbial homeostasis and can contribute to the onset or progression of CVDs through dysbiosis. The authors discuss the association between oral microbiota and CVDs, highlighting how periodontal diseases can lead to systemic inflammation and contribute to atherosclerosis. The article outlines the application of engineered bacteria in treating CVDs, including obesity, hyperlipidemia, diabetes, and IBD. Genetically modified bacteria can express beneficial traits such as N-acylphosphatidylethanolamines to resist obesity, secrete antioxidants to prevent liver oxidative damage, and produce glucagon-like peptide-1 (GLP-1) to regulate glucose metabolism and reduce blood pressure. The use of synthetic biology tools allows for precise control over bacterial interactions with the host, enhancing the effectiveness and safety of these therapies. The potential of engineered oral probiotics and pathogenic bacteria is also discussed, emphasizing the versatility of the oral microbiome as a target for microbial engineering. Oral probiotics like *Lactobacillus* strains can be engineered to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues. Oral pathogens associated with CVDs can be modified through protein and genetic engineering to reduce their virulence and promote beneficial effects. Despite the promising prospects, the authors acknowledge challenges such as bacterial virulence, genetic instability, and the need for regulatory compliance. They highlight the importance of continued research and technological advancements to overcome these hurdles and develop more effective and safe engineered oral microbiota therapies for CVDs.