Abstract: Provided herein are systems and methods for enhancement of polyphenols, such as chlorogenic acids, chicoric acid, anthocyanins, and water-soluble quercetin derivatives, production in red lettuces. Also provided are transgenic lettuce for the production of polyphenols. Also provided are parts of such transgenic lettuces, such as seeds leaves, and extracts. The disclosure also provides methods of using the new lettuces and parts thereof for protection against viral/bacterial infection (i.e., by inhibiting activities of COVID-19 virus/enzymes) diabetes, cardiovascular diseases, memory and eyesight loss, inflammation, and cancer.